REGENERATIVE MEDICINE illustration © UCL Expertise, Resources and Innovation Capacities of BioWin Members BIOWIN MAKING SCIENCE AND BUSINESS PARTNERSHIPS A SUCCESS A HISTORY OF EXCELLENCE A WEALTH AND DIVERSITY OF ACTORS BioWin is one of Wallonia’s 6 competitiveness clusters, implemented in 2006 as part of the region’s overall Marshall Plan to develop Wallonia as a centre able to bring innovation to the market. BioWin is the Health Cluster of Wallonia, federating some 510 regional actors, large and small, and focussed on four strategic axes – Open Innovation; Talent and Expertise; Technological Platforms and International Partnerships. In all, the member companies of BioWin generate over 3.4 billion euros in annual revenues, and employ over 12,500 people from all over the world. Its companies range from global market leaders to highly specialised SMEs for whom the BioWin cluster is fertile ground for advanced research and development. On the academic side, three academic institutes, involving no less than five universities, include the Université Catholique de Louvain (UCL), the Université Libre de Bruxelles (ULB) and the University of Liège (ULg) as well as their public medical facilities. Prestigious research institutes are also in place to partner with industry. Between them, these universities and research institutes employ over 11,000 researchers and bring funding, clinical trials facilities and a wealth of highly trained and specialised human resources. BioWin’s strategy of federating regional actors is based on the recent and successful history of collaborations between industry, academia and the region. Industry leaders such as GSK Vaccines, UCB and IBA have all grown out of the local scientific and industrial scene, while Baxter has been present in Wallonia for more than 30 years. The region and its academic institutes and research centres have developed synergies with these and other companies over the years, and this has led to the positioning of Wallonia as a centre of health sciences excellence, attracting talents, business and investment as it continues to grow. HEALTH’S INNOVATION VALLEY The Health Cluster of Wallonia boasts over 100 health science companies and a high concentration of universities, medical facilities and research institutes, and is a veritable hub of health sciences innovation and development in Europe. BioWin’s worldwide reputation as an environment where science and business go hand in hand is cemented by the region, whose support and investment have enabled BioWin members become European leaders in specific health domains with a growing international reputation: Biopharmacy, Radiopharmacy, Diagnostics, Biotech products, Medical Devices and Equipments. ADDED-VALUE PARTNERSHIPS The region’s successful partnering of industry with research and academic facilities has created a value chain that allows new products and techniques to be generated, developed and brought to global markets. For example, Belgium has the world’s highest proportion per capita of clinical trials, has the fastest approval time for phase 1 clinical trials in Europe (within 14 days), thanks to the country’s favourable regulatory environment. Supporting this ambitious development initiative is a multilevel approach to funding: public university funding, European institutional funding, private funding and Walloon regional funding all combine to ensure that the healthcare innovations developed in Wallonia are extended to a world market. REGENERATIVE MEDICINE AND THE VALUE CHAIN HOW GENERATING SYNERGIES CREATES MEDICAL INNOVATIONS The density and quality of health science actors in the region has created a ‘value chain’ that stimulates innovation and excellence, and allows the region to develop unique and highly specialised capacities in new health science areas. Regenerative medicine is one such area, here led by an industry group made up of 7 research and development companies, 3 of which are in Phase II and III trials. These are Promethera BioSciences, Bone Therapeutics and Cardio 3 BioSciences – specialised in liver, bone and heart cell regeneration technology respectively. These companies and the synergies created with the neighbouring academic and research centres as well as support groups in the BioWin value chain, place the region at the forefront of research and development in a field whose importance cannot be underestimated. HOW THE VALUE CHAIN WORKS BioWin contains a critical mass of specialists capable of developing regenerative medicine, which include research excellence centres, clinical expertise centres, biobanks and tissue banks on the academic and research side, and cell therapy companies as well as CROs and CMOs on the industry side. On top of that, this value chain is completely integrated thanks to cultural and geographical proximities that foster partnerships between different expertises. This makes Wallonia a place to be for innovation. The many available university hospitals make translational research more effective through close connections between research laboratories and clinicians that facilitate the back and forth process of this approach. Moreover, clinical expertise centres have technological capacities and know-how to conduct 1st in men studies, which is of real added value to achieve proof of concept for new regenerative medicine products. GENERATING OPTIMUM SYNERGIES Thus, the value chain creates the optimum conditions to bring new products to a market that is in constant need of health innovations. Wallonia – as substantial investor in R&D, as provider of know-how and as regional development agency – is a strong supporter of this emerging sector. BioWin’s role therefore is essentially based on its four strategic axes: • Supporting open innovation between members by helping in the formation of consortia via networking activities as well as ensuring good governance practices in the funded projects. • Providing training and expertise (such as BioCell) to develop both business and industry capacities, building bridges between the two as well as meeting the recruitment expectations of the Health sector in Wallonia. • Creating shared technology and innovation platforms (such as MaSTherCell) aimed at manufacturing new products, treatments, innovative process or services to the market. • Pursuing international opportunities, both in terms of partnerships and product/expertise exports, in collaboration with the Wallonia Export and Investment Agency (AWEX). REGENERATIVE MEDICINE A EUROPEAN INNOVATION PRIORITY BioWin is also a member of initiatives such as TERM (Tissue Engineering and Regenerative Medicine), a Europe-wide project supported by the EU’s DG Research and aimed at developing a culture of applied innovation and partnership across seven EU regions containing 13 centres of excellence in the field of regenerative medicine. Regenerative medicine is an ‘innovation priority’ in meeting the medical, societal and economic challenges of a rapidly ageing European population, as well as being a key development area in preventive medicine. With its main aim to switch the medical focus from treatment to cure, regenerative medicine is an area that holds great promise both in terms of improving people’s long-term health, and of balancing the costs of treatment. For BioWin it is also an important economic opportunity, providing scope for development as a key scientific and industrial innovator in a field which importance is set to increase exponentially. REGENERATIVE MEDICINE IN WALLONIA FROM BENCH TO MARKET ACADEMIC / CLINICAL OUTPUTS Bone Cartilage ACADEMIC EXCELLENCE IN RESEARCH CENTRES Pancreas Marrow Proof of Concept (in vitro & in vivo) and patents. Brain Skin Liver Heart CLINICAL ACADEMIC EXCELLENCE UCL, ULB, ULg UMons, UNIVERSITE DE NAMUR CLINICAL EXPERTISE CENTRES BIOBANKS AND TISSUES BANKS FIRST IN PATIENTS PRIVATE / PUBLIC INNOVATION PARTNERSHIPS TRANSLATIONAL RESEARCH BioWin Cell Therapy Companies INDUSTRIAL EXCELLENCE BIG BIOPHARMACEUTICALS SME's Pre-Clinical study & model Contract Research Organisations Production (clinical batches) Clinical Trials Services Providers Clinical study Production (commercial batches) Contract Manufacturing Organisations INDUSTRIAL OUTPUTS • Logistics • Quality Assessment • Quality Control • Regulatory Affairs Cell Therapy Products Bone Liver Heart R…G…N…RATIV… M…DICIN… Table of contents COMPANIES info sheet info sheet Bone Therapeutics Masthercell Cardio3 Biosciences Promethera Biosciences KitoZyme Synolyne Lonza LABORATORIES info sheet info sheet UCL - Cardiovascular Research ULB - Laboratory of Bone Biochemistry and Metabolism Rheumatology and Physical Medicine Dept UCL - CRIBIO ULB - Laboratory of Clinical Cell Therapy UCL - Endocrine Cell Therapy Unit (1) GIGA Tech Platforms UCL - Endocrine Cell Therapy Unit (2) ULg - Biomechanics Research Unit UCL - Experimental Surgery Laboratory ULg - Bone and Cartilage Research Unit UCL - Genetics ULg - Centre Interfacultaire des Biomatériaux UCL - Gynaecology ULg - Genetics (CHU Liège) UCL - Hematopoiesis Unilab Lg - Hematology UCL - Hepato-gastroenterology Liver & Pancreas Development ULg - Hematology Unit of the GIGA Research Institute UCL - Imaging ULg - Laboratory of Cell and Gene Therapy (CHU) UCL - Neuropharmacology and Neurodifferentiation ULg - Laboratory of Thrombosis and Hemostasis, GIGA Research Institute UCL - Pediatric Hepatology and Liver Cell Therapy ULg - Laboratory of Experimental Pathology UCL - Spinal Cord and Dental Regeneration UMons - CIRMAP ULB - IRIBHM (1) UMons - Human Biology & Toxicology Laboratory ULB - IRIBHM (2) University of Namur (FUNDP) - Research Unit in Cell Biology ORGANISATIONS info sheet PLATFORMS Biopark Formation CMMI LIEU sCINNAMIC - Centre for Innovation in Medicine (CIM) info sheet ORGANISATION Promethera Biosciences MasTherCell Phase II 2013 Lonza 2013 PAGE PRODUCTION OF COMMERCIAL BATCH PRODUCTION OF CLINICAL BATCH INDUSTRIAL (PRE)CLINICAL DEVELOPMENT EXPLORATORY (PRE) CLINICAL DEVELOPMENT BASIC / APPLIED RESEARCH COMPANIES Summary table Bone Therapeutics Phase III 3 Cardio3 BioSciences Phase III 4 5 6 7 COMPANIES REGENERATIVE MEDICINE REGENERATIVE MEDICINE COMPANY R…G…N…RATIV… M…DICIN… Bone Therapeutics Stem cells Bone & Joint Heart Failure Cell(HF) Therapy Osteoarticular diseases Osteonecrosis Non-union fractures Maxillofacial Allogeneic Autologous Headquartered at the Biopôle of Gosselies (South of Brussels, Belgium), Bone Therapeutics is a leading international biotechnology company specialized in the treatment of osteo-articular diseases using cell therapy. The Company’s strategic position in skeletal tissue repair and regeneration is supported by an outstanding knowledge of the bone physiology and pathophysiology in major diseases as well as in niche indications, the pioneering works of its founders in stem cell transplantation in humans and a long-standing expertise in cell therapy clinical trials and regulatory affairs. The Company combines the expertise of a « minipharma » with the flexibility of a SME and covers: pharmaceutical R&D (in vitro & in vivo pharmacology), production, clinical development and regulatory affairs. PRODUCTS Bone Therapeutics develops innovative cell products for the repair and regeneration of bone and joint tissues in various indications. The Company’s technology platforms, developed over more than 10 years of extensive basic research, enable adult stem cell isolation, expansion and differentiation. The Company’s products (autologous & allogeneic) are expected to have a number of significant commercial and medical/technical advantages. The Company has worldwide exclusive rights for a series of patents and technologies related to osteogenic differentiation of stem cells, identification and tools for implantation. Based on the promising results of phase I/II clinical studies, the Company’s lead product, PREOB®, is currently in 2 phase III pivotal trials in Europe (treatment of osteonecrosis and non-union fractures). TARGETED MARKET Bone disease market is one of the largest healthcare markets worldwide. In the bone reconstruction segment, there are annually in Europe & USA over 4 million procedures requiring bone grafts. The non-union fracture market together with spine fusion markets are worth 2.5 billion USD annually. Cell therapy should apply to up to half of the total bone graft market, for a potential of 2 million (orthopaedic and maxillofacial) annual procedures. The Company is best positioned in applications such as delayed union, non-union fractures, large bone defects and other orphan bone diseases, because of its product, expertise & patient access. PARTNERSHIPS/COLLABORATIONS Bone Therapeutics has several research collaborations with industrial and academic partners (supported by Wallonia Region): ULB (Belgium) (Department of Rheumatology - Hôpital Erasme - Prof. Gangji ; Laboratoire de Pharmacie Galénique et de Biopharmacie - Prof. Amighi) ; ULg (Belgium) (Department of Rheumatology - CHU Sart-Tilman - Prof. Malaise ; GIGA-R - Immunology and Infectious Diseases Unit - Prof. Moutschen) KEY FIGURES Staff: 37 employees (+11 in direct collaboration) 2 Orphan Drug Designations, 7 own and 6 in-licensed Patents, 2 Trademarks Capital & Fundraising: 17.254.320 EUR Development stage: 2 Phase III trials ongoing Bone Therapeutics s.a./n.v. | Rue Adrienne Bolland 8 | 6041 Gosselies | Belgium | www.bonetherapeutics.com Enrico Bastianelli | Chief Executive Officer | T. +32 (0)2 529 59 90 | F. +32 (0)2 529 59 93 [email protected] 2 COMPANY R…G…N…RATIV… M…DICIN… CARDIO3 BIOSCIENCES Cardio3 BioSciences is a Belgian leading biotechnology company focused on the discovery and development of regenerative and protective therapies for the treatment of cardiac diseases. The company was founded in 2007 and is based in the Walloon region of Belgium. Cardio3 BioSciences leverages research collaborations in the US and in Europe with Mayo Clinic and the Cardiovascular Center Aalst, Belgium. Stem Cells cells Heart Failure (HF) Acute Myocardial Infarction (AMI) PRODUCTS The Company’s lead product candidate C3BS-CQR-1 is an innovative pharmaceutical product that is being developed for HF indication. It consists of a patient’s own cells that are harvested from the patient’s bone marrow and engineered to become new heart muscle cells that behave identically to those lost to heart disease. Other research programs and product candidates targeting HF and AMI are in development, based on the breakthrough Cardiopoiesis technology platform.The company has also developed C-Cath®ez, the most technologically injection catheter with superior efficiency of delivery of bio therapeutic agents into the myocardium. TARGETED MARKET Heart Failure and Acute Myocardial Infarction – Worldwide Cardio3 BioSciences estimates that, out of a world population of 5.2 billion people in the regions traditionally targeted by pharmaceutical and medical device companies, 117 million people are suffering from HF worldwide, and that this number is believed to double by 2020 as the incidence is rising for a variety of reasons including lifestyle factors and the increasing life expectancy of patients PARTNERSHIP/COLLABORATION Cardio3 BioSciences enjoys academic and clinical collaborations with Mayo Clinic, USA and the Cardiovascular Center, Aalst, Belgium.The company has entered industrial collaborations with ATMI and Creganna KEY FIGURES • Founded in 2007 • 54 people • 46 mio € funding Cardio3BioSciences | 12 rue Edouard Belin | 1435 Mont-Saint-Guibert | Belgium | [email protected] / www.c3bs.com Anne Portzenheim | Communication Manager | +32 (0)10 39 41 00 | +32 (0)10 39 41 41 | [email protected] 3 COMPANY R…G…N…RATIV… M…DICIN… LONZA Lonza offers world class technology platforms in the area of GMP cell culture and viralbased therapeutic manufacturing, custom therapeutic culture media, as well as full line of custom bioassays. Our extensive experience in cell and gene therapy process optimization and scale up innovation helps clients to safely and effectively advance their products through all phases of the commercial pipeline and maximize their return on investment. Scale Up Stem cells Scale Out HeartDevelopment Failure Process (HF) GMP Compliance Cell Therapy Viral Therapy Allogeneic Autologous PRODUCTS • Service Offerings: • Product Development • Cell Therapy Manufacturing • Viral Therapy Manufacturing • Clinical-Grade iPSCs and Derived Cell Types • Custom Therapeutic Media • Testing Solutions • Tissue Acquisition TARGETED MARKET • Cell Therapy Developers • Viral Therapy Developers • Biotechnology • Biopharmaceuticals PARTNERSHIP/COLLABORATIONS With established production capacities in North America, Asia and Europe, Lonza has established local and global collaborations with Biotech and major Biopharmaceutical companies active in the field of Regenerative Medicine. KEY FIGURES In 2011, Lonza had sales of CHF 2.692 billion Lonza has 45 major production and R&D facilities world wide Lonza employs over 11,000 people world wide Lonza Verviers SPRL | Parc Industriel de Petit-Rechain | BE - B-4800 Verviers | http://www.lonza.com Samanta Cimitan PhD | Business Development Therapeutic Cell Solutions [LBS Services] Lonza AG | Münchensteinerstrasse 38 | CH | 4002 Basel | T. +41 61 3168375 mail to: [email protected] | [email protected] 4 COMPANY R…G…N…RATIV… M…DICIN… MaSTherCell MaSTherCell, Manufacturing Synergies for Therapeutic Cells, a cell therapy dedicated Contract Development and Manufacturing Organization (CDMO) located in the Biopark in Gosselies, has been founded in November 2011.The company offers its services to cell therapy product development companies in need of process development expertise or clinical trial and/or commercial GMP manufacturing capacity. Contract Stem cells Development Heart Failure Contract (HF) Manufacturing GMP Cell Therapy SERVICES MaSTherCell dedicates all its efforts and facilities to the development and manufacturing of cell therapy products for its customers. TARGETED MARKET Though we focus primarily on Europe, we are in contact with several US prospects. We are also considering direct access to US facilities, either through collaboration with a US partner or by going direct. We will soon start prospection in Asia. PARTNERSHIP/COLLABORATIONS We have already established several collaborations with Belgian partners like ImmuneHealth, and have the intention to further develop partnerships with experts in order to offer the best services to our customers, covering the entire supply chain. KEY FIGURES Masthercell currently employs 11 people and will have 20+ people in 2014 Over 5.5 M€ raised. Expected revenues of 3M€ by end 2014 Masthercell SA | Rue Adrienne Bolland, 8 | B-6041 Gosselies | Belgique | www.masthercell.com Patrick Stragier Chief Business & Technology Officer | [email protected] 5 COMPANY R…G…N…RATIV… M…DICIN… PROMETHERA BIOSCIENCES cell-based medicinal product, advance therapy medicinal product, biotechnology, pediatric, orphan drug. Stem cells Heart Failure (HF) Liver inborn metabolic diseases Crigler-Najjar syndrome Urea Cycle disorders Liver Fibrosis Promethera® Biosciences is a Belgian pharmaceutical company, spin-off from the Université Catholique de Louvain which develops innovative treatment based on allogeneic adult stem cell technology.Promethera® Biosciences' mission is to discover, develop, manufacture and commercialize innovative cell therapy products to treat liver diseases using allogeneic progenitor cells harvested from healthy human livers.Promethera® Biosciences was founded in 2009 based on research discovery by Professor Etienne Sokal's team (UCL, Brussels). Eric Halioua is the Chief Executive Officer and co-founder of Promethera® Biosciences. PRODUCTS Promethera® Biosciences develops two products based on a patent-protected progenitor cell type, the Heterologous Human Adult Liver Progenitor Cell (HHALPC): • Promethera® HepaStem is a cell therapy product indicated in severe liver diseases affecting children and adults. A wide variety of inborn metabolic diseases and acquired chronic hepatic diseases can be treated with the same product. • Promethera® HepaScreen is a durable cell-based assay for the pharmaceutical industry. The pre-clinical cell model is designed to evaluate the metabolism and detoxification of new drugs by the human liver. TARGETED MARKET The potential market of the cell-based medicinal product HepaStem is the population suffering either from one of 200 liver-based inborn metabolic diseases or from chronic liver diseases. In Europe and in the USA, inborn diseases affect a total of 210 000 patients, with 10 000 new cases each year. Chronic liver diseases affect 300 000 patients of whom 20% are affected by liver fibrosis. The total market is estimated at EUR 100M for the cell-based assay HepaScreen, designed for the metabolic and toxic evaluation of new chemical entities by pharmaceutical companies. PARTNERSHIPS/COLLABORATIONS Industrial and academic partners include UCB pharma (development of HepaScreen), Artelis-ATMI (innovative manufacturing processes), CER Groupe (Centre d’Economie Rurale, CRO), Université Catholique de Louvain (Laboratoire d'Hépatologie Pédiatrique et Thérapie Cellulaire), Universiteit Hasselt, and Faculté Notre Dame de la Paix Namur. KEY FIGURES Promethera Biosciences is a fast growing company. The motivated team expanded from two employees in 2009 to 46 in June 2012, directed by a seasoned management board. The GMP-accredited 327 m² pilot plant includes three grade B aseptic rooms. Promethera Biosciences | rue Granbonpré 11 | 1435 Mont-Saint-Guibert | http://www.promethera.com Eric HALIOUA, CEO | T. +32 (0)10 39 43 00 | F. +32 (0)10 39 43 01 | [email protected] 6 LABORATORIES PAGE CLEAN ROOMS CLINICAL RESEACH PRECLINICAL RESEARCH ORGANIZATION BASIC RESEARCH Summary table UCL – Cardiovascular Research 9 UCL – Pediatric Hepatology and Liver Cell Therapy 10 UCL – Gynaecology 11 UCL – …ndocrine Cell Therapy Unit (1) 12 UCL – …ndocrine Cell Therapy Unit (2) 13 UCL – …xperimental Surgery Laboratory (ISO9001 for advanced cell therapies) 14 UCL – Neuropharmacology and Neurodifferentiation 15 UCL – Hematopoiesis 16 UCL – Spinal Cord and Dental Regeneration 17 ULB – IRIBHM (1) 18 ULB – IRIBHM (2) 19 ULB – Laboratory of Bone Biochemistry and Metabolism-Rheumatology and Physical Medicine Dept. 20 Ulg – Laboratory of Cell and Gene Therapy - CHU 21 ULg – Hematology Unit - GIGA Research Institute 22 ULg – Laboratory of Thrombosis and Hemostasis - Giga Research Institute 23 ULg – Bone and Cartilage Research Unit 24 University of Namur (FUNDP) – Unit Research in Cell Biology 25 LABORATORIES REGENERATIVE MEDICINE REGENERATIVE MEDICINE LABORATORY R…G…N…RATIV… M…DICIN… UCL - Gynaecology Stem cells Female and Male Heart Failure Infertility (HF) Germ Cell Cryopreservation Cryostorage Grafting The Gynaecology unit is a pluridisciplinary team comprising gynecologists, biochemists and a veterinary surgeon, that works in close collaboration with clinical teams to manage infertility problems and treat gynecological disorders. The research laboratory is equipped with all the setting for cell culture, microscopy and image analysis, immunohistochemistry and molecular biology and has at its disposal UCL technology platforms. It is ideally located, close to the ovarian and testicular tissue biobanks and the Cliniques Universitaires St Luc, where thousands of patients are treated for infertility problems each year and clinical trials are conducted. RESEARCH AXES / TECHNOLOGY There are to main fields of interest associated with female and male infertility: • Optimization of protocols for human ovarian tissue and follicle cryopreservation and transplantation in order to preserve fertility in cancer patients. • Establishment of cryopreservation protocols for immature testicular tissue, designed to preserve spermatogonial stem cells with a view to restoring fertility in young boys after gonadotoxic treatment for cancer. Technologies developed include male and female germ cell cryopreservation, experimental in vitro and in vivo models, and analytical tests to evaluate cell viability and functionality after cryostorage and/or grafting. APPLICATIONS FIELDS Experimental research: Set-up of new protocols for stem cell and germ stem cell cryobanking and transplantation. Clinical application: Development of new options to preserve fertility in men and women undergoing gonadotoxic treatments. Biopharmaceutical industry: Design of innovative tools to transplant isolated cells and tissues ONGOING PROJECT(S) • Assembly of an artificial ovary combining isolated human ovarian follicles, fibrin and a textile pocket (Biowin). • Characterization and differentiation of male primordial germinal cells derived from induced pluripotent stem cells, in order to restore fertility in cancer patients undergoing radio- and/or chemotherapy. Université catholique de Louvain / Pôle de Gynécologie / Institute of experimental and clinical research (IREC) Avenue Mounier 52, Box B1.52.02 | B-1200 Brussels | www.saintluc.be/services/medicaux/gynecologie/index.php Andrology | Prof Christine Wyns, MD, PhD | +32 (0)2 764 65 76 | [email protected] Gynaecology | Anne Van Langendonckt, MSc, PhD | +32 (0)2 764 52 87 | [email protected] Prof Marie-Madeleine Dolmans, MD, PhD | +32 (0)2 764 41 14 | [email protected] 10 LABORATORY R…G…N…RATIV… M…DICIN… UCL - Endocrine Cell Therapy Unit (1) Monolayer Stem cells Cellular Heart Failure Device (HF) Human islets Encapsulation Type 1 Diabetes Although islet allotransplantation represents a useful therapeutic tool for Type 1 diabetic (T1DM) patients, the need for permanent immunosuppresion remain, however, as major hurdle to the widespread use of pancreatic islet transplantation for curing type 1 diabetes mellitus. Therefore, our clinical research focused on the immunoprotection of human islets allotransplantation by encapsulation to perform: (i) a simple, (ii) safe, (iii) reversible and (iv) functional procedure to control a brittle type 1 diabetes. RESEARCH AXES/TECHNOLOGY Our research work focused on the production of a Monolayer Cellular Device to encapsulate human islets in view to (i) obtain a selective permeability for small molecules (glucose, oxygen,…) avoiding the passage of molecules over 150 KDal (as IgG, IgM, Complement,….) and (ii) perform a clinical simple procedure with subcutaneous transplantation. Clinical development of the transplantation of encapsulated human allogenic islets in the subcutaneous tissue following: (i) the regulation of “Advanced Therapy of Medicinal Products” and (ii) with a certification ISO9001-2008. This clinical research program is performed under “GMP-like” (Grade A in Grade B) and ISO9001-2008 certifications for the quality program. APPLICATION FIELDS The Monolayer Cellular Device for human islets encapsulation is performed to control brittle type 1 diabetes with a minimally invasive procedure. The products of the invention may be useful not only for islets encapsulation but also for other endocrine cells (parathyroid cells,…). ONGOING PROJECT(S) A Phase 1 clinical study (15 patients) is currently performed to assess the safety and efficacy of the Monolayer Cellular Device (for allogenic encapsulated human islets) following the guidelines of the Belgian Ministry of Health, approved by the local (of the Medical Faculty, Université Catholique de Louvain) and by national ethical committee for clinical study (EUDRACT number: 2008-001758-41). Université catholique de Louvain Endocrine Cell Therapy Unit | Cliniques universitaires Saint-Luc | B-1200 Brussels (Woluwe) | Belgium Denis Dufrane | Head of Unit | +32 (0)2 764 67 86 | [email protected] 11 LABORATORY R…G…N…RATIV… M…DICIN… UCL - Endocrine Cell Therapy Unit (2) Autologous Stem cells AMSCs Heart Failure (HF) Bone Adipose stem cells 3-Dimensional graft Bone repair Tissue engineering is a growing field where new materials are being developed for implantation into the body. One important area involves bone graft materials to replace areas of bone lost to trauma or disease (as e.g. tumor resection). Therefore, the production of multi-dimensional tissues for use in bone graft, reinforcement or reconstruction remains a real technical issue.Our work focused on the clinical development of a multi-dimensional osteogenic-like structure made of autologous adipose mesenchymal stem cells (AMSCs). RESEARCH AXES/TECHNOLOGY Our research is directed to the field of AMSCs, (i) their GMP-isolation with a minimally invasive subcutaneous procedure, (ii) their differentiation into multi-dimensional tissues and (iii) characterization (osteogenic phenotype,genetic stability,endotoxin/mycoplam content) in view to obtain: the same properties as a real bone, an non-immunogenic effect, a desirable handling and mechanical characteristics required for implantation in the bone native disease area. This clinical research program is performed under “GMPlike” (Grade A in Grade B) and ISO9001-2008 certifications for the Advanced Therapy Medicinal Product regulation APPLICATION FIELDS The products of the invention may be useful in bone tissue reconstruction, especially traumatology, orthopaedic, plastic, maxillofacial and neurosurgery. ONGOING PROJECT(S) Clinical application (safety and efficacy) of this autologous osteogenic-like structure (derived from adipose tissue) is under investigation in orthoapedic surgery (after tumour resection and in the treatment of congenital pseudarthrosis) and in neurosurgery (for vertebral body fusion). Université catholique de Louvain Endocrine Cell Therapy Unit | Cliniques universitaires Saint-Luc | B-1200 Brussles (Woluwe) | Belgium Denis Dufrane | Head of Unit | +32 (0)2 764 67 86 | [email protected] 12 LABORATORY R…G…N…RATIV… M…DICIN… UCL - Experimental Surgery Laboratory Stem cells Diabetes Heart Failure Xeno-islets (HF) Pig islets Insulin-producing cells, Transgenic/Cloned pigs, Bioartificial pancreas, Alginate encapsulation Since pancreas or islets transplantation are not accessible for the majority of diabetic patients due to the organ shortage and the need for chronic immunosuppression, research needs to focus on alternative insulin-producing cells and ways to implant these cells without the use of chronic immunosuppression. Alginate Encapsulation of pig islets cells is a possible way to solve both problems: the source of pig cells would in fact be illimited and the encapsulation (micro or macro) can protect these cells from the recipient immune system. RESEARCH AXES/TECHNOLOGY All in vivo models to evaluate diabetes correction by islets transplantation (rodents, pigs, higher mammals,...). (ii) Islets isolation from rodents, adult or neonates pigs. (iii) Production of transgenic and cloned pigs to provide “super pig islets”. (iv) Micro and Macro-encapsulation with different kind of extra-pure alginate. -Bioartificial pancreas APPLICATION FIELDS Diabetes mellitus type 1 is a chronic disease affecting 30 millions peoples in the world and type 2 diabetes concern 220 millions of peoples around the world. The latter disease will be the “disease of the century”. According to the World Health Organisation (WHO), direct healthcare costs of diabetes-related illnesses range from 2.5% to 15% of a country’s annual healthcare budget. If the predicted increase in cases of diabetes is borne out, the cost will increase to 212–391 billion € by 2025 (IDF Diabetes Atlas, 2006). ONGOING PROJECT(S) • Pig islets transplantation after micro or macro-encapsulation in diabetic higher mammals • Production of transgenic or cloned pigs • Development of bioartificial pancreas Université catholique de Louvain Experimental Surgery Laboratory | Avenue Hippocrate 55 bte B1.55.04 | B-1200 Brussels (Woluwe) | Belgium Pierre Gianello | Laboratory of Experimental Surgery, UCL, Brussels, Belgium [email protected] | +32 (0)2 764 55 82 Denis Dufrane | laboratory of Experimental Surgery, UCL, Brussels, Belgium | [email protected] Sophie Veriter | Laboratory of Experimental Surgery, UCL, Brussels, Belgium | [email protected] 13 LABORATORY R…G…N…RATIV… M…DICIN… UCL - Neuropharmacology and Neurodifferentiation Spinal cord Stem cells Glial cells Heart Failure Mesenchymal (HF) stem cells Neural progenitor Neurodegenerative disease Neuroprotection The groups of Neuropharmacology and Neurodifferentiation within the Institute of Neuroscience joint their efforts in the study of cellular and molecular mechanisms involved in the development of the central nervous system and the progression of neurological disorders. Research project are focused on the spinal cord, in which we study the dysfunctions of neurons and glial cells in amyotrophic lateral sclerosis (motoneuron disease) or in models of physical or nervous lesions resulting in chronic pain. We also examine the putative reactivation of key developmental process upon nervous lesions. RESEARCH AXES / TECHNOLOGY The groups have complementary expertises for in vitro and in vivo characterization of neural cell progenitors during central nervous development and in the study of glial cell function in models of nervous lesions. Beside DNA cloning and other conventional biochemical techniques, key experimental approaches are primary neural cell cultures, immunohistochemistry and in situ hybridization, rodent neurosurgery and analysis of animal behaviours (diverse motor and pain tests). Projects are conducted on dedicated transgenic animal models showing impaired development of developing neurodegenerative disorders. In the context of regenerative medicine, we study the activation of neuroprotective properties of endogenous glial cells during the progression of amyotrophic lateral sclerosis or in the context of neuropathic pain. In these animal models, we also examine the neuroprotective/neuroimmunomodulatory properties of bone derived mesenchymal stem cells. APPLICATIONS FIELDS A better knowledge of the neuroprotective or immunomodulatory profile of bone marrow derived mesenchymal stem cells hold clue for the development of regenerative medicine for neurological disorders. Supporting endogenous repair or defense mechanisms, the systemic or intrathecal administration of stem cells constitutes a putative therapeutic approach of nervous disease involving neuroinflammation. ONGOING PROJECT(S) In vitro characterization of the neuroprotective profile of mesenchymal stem cells.Influence of grafted mesenchymal stem cells on the inflammatory response in models of spinal cord insults. Mechanisms of mesenchymal stem cell recruitment at nervous lesion site Université catholique de Louvain UCL – Institute of Neuroscience (IoNS) | Woluwe / B-1200 Brussels (Woluwe) | Belgium | www.uclouvain.be/en-ions.html Group of Neuropharmacology / Emmanuel Hermans | Professor | +32 (0)2 764 93 39 (or 54 10) [email protected] Lab of Neural differentiation / Frédéric Clotman/ Professor / +32 (0)2 764 55 71 | frederic.clotman @uclouvain.be 14 LABORATORY R…G…N…RATIV… M…DICIN… UCL - Hematopoiesis Stem cells Hematopoietic stemFailure cells, Heart Cord blood (HF) Hematopoiesis JAK-STAT, JAK2 V671F, MPL/TpoR, PDGFR Interferon, myeloproliferative neoplasms, The groups study normal and pathological hematopoiesis, especially in relationship with myeloid cancers, leukemia and cord blood cell differentiation. Research is conducted in two units of the de Duve Institute and in the St Luc Hospital, where a blood cancer bank has been initiated. Both the Hematology and Clinical Biology departments are involved with the fundamental units of the de Duve Institute, where multicolor FACS analysis and sorting, sequencing, mass spectrometry and in vivo mouse bone marrow transplant approaches are employed. The groups are known for identification of medically important mutations, such as JAK2 V617F, JAK1 mutants, thrombopoietin and PDGF receptor mutants and for novel approaches to therapy, especially cellular therapy and cord blood cell differentiation. Physiologic and pathologic hematopoiesis are studied and compared. RESEARCH AXES / TECHNOLOGY The major axes of research are: i) identification of the molecular bases of myeloid cancers; ii) study of the signaling and biologic effects of cytokine receptors, Janus kinases and tyrosine kinase receptors; iii) study of the mechanism of the antiproliferative effect of type I interferon in myeloid cancers; iv) signaling by cytokine receptors and Janus kinases in hematopoietic stem cells in physiologic and myeloproliferative hematopoiesis; v) effect in vivo in myelofibrosis patients of JAK2 inhibitors; vi) development of novel systems to study hematopoiesis using cord blood cells; vii) cell therapy models with cord blood cells. APPLICATIONS FIELDS Hematology, Oncology, Endocrinology, Transfusion medicine, Transplantation ONGOING PROJECT(S) The major projects explore the role of the cytokine receptor, JAK-STAT and tyrosine kinase receptors (PDGFR and mutants) in physiologic and pathologic hematopoiesis. Both cell lines and in vivo mouse models are used, along with retroviral transduction of primary patients, mouse and cord blood cells. The broad aim is to identify the precise signaling mechanisms responsible for myeloid cell differentiation and understand how oncogenic proteins such as JAK2 V617F or PDGR-fusion proteins induce myeloid cancers. Université catholique de Louvain Cell Signaling (SIGN) | de Duve Institute |http://www.deduveinstitute.be Stefan Constantinescu / Professor |+32 (0)2 764 7540 |[email protected] Growth factors receptors | de Duve Institute Jean-Baptiste Demoulin / Professor | +32 (0)2 764 6529 | [email protected] Hematology | St Luc Hospital and de Duve institute Laurent Knoops / MD, PhD | +32 (0)2 764 1807 | [email protected] Hematological Clinical Biology | St Luc Hospita Dominique Latinne / Professor and Head of Hematological Clinical Biology +32 (0)2 764 6788 | [email protected] Division of Haematology, Haemostasis and Thrombosis Unit, and Haemophilia Clinic - St Luc Hospital | B-1200 Brussels Cédric Hermans / Professor and head of Division of Hematology | +32 (0)2 764 1785 [email protected] | http://www.hemophilie-ucl.be 15 LABORATORY R…G…N…RATIV… M…DICIN… UCL - Spinal Cord and Dental Regeneration Our group focuses on drug delivery systems that address unmet pharmaceutical and medical needs, including drug delivery in tissue engineering. We develop 3D implants (hydrogels, polymeric scaffolds) delivering growth factors, genes, drugs and/or cells that provide sustained delivery of factors, support survival, infiltration and/or proliferation of cells for tissue engineering applications, in particular for spinal cord injury and for dental regeneration. Stem cells Dental Heart StemFailure cells (HF) Drug Delivery Scaffolds Injectable Hydrogels Biomaterials RESEARCH AXES / TECHNOLOGY • Injectable hydrogels • Scaffold, Stem cells • Growth factor delivery (nanoparticles, microparticles) APPLICATIONS FIELDS • Spinal cord injury • Dental regeneration ONGOING PROJECT(S) • Development of biomaterials for regenerative medicine and dentistry • Influence of dental stem cells on spinal cord regeneration Université catholique de Louvain Louvain Drug Research Institute Pharmaceutics and Drug Delivery Unit | B-1200 Brussels (Woluwe) | Belgium www.uclouvain.be/en-269736.html Anne des Rieux/ Chercheur Qualifié FNRS | +32 (0)2 764 73 57 | [email protected] Julian Leprince/ Chargé de Recherche FNRS | +32 (0)2 764 57 50 | [email protected] 16 LABORATORY R…G…N…RATIV… M…DICIN… ULB - IRIBHM (1) One major challenge for neurological diseases is the lack of appropriate models that mimick all aspects of the human condition. Another major issue in brain therapy is the advent of rational brain repair strategies. Both issues could be solved in principle through the use of pluripotent stem cell technology, coupled with directed neural development. Disease modelling Stem cells Heart Failure Induced pluripotent (HF) stem cells Embryonic stem cells Brain repair Cerebral cortex Neurodegeneration Epilepsy RESEARCH AXES/TECHNOLOGY Our laboratory has pioneered the technology to direct the differentiation of embryonic or induced pluripotent stem cells into defined population of neurons of clinical relevance, in particular neurons of the cerebral cortex ((Gaspard et al. Nature 2008; European Patent Application 11184863.6). These neural cells recapitulate most of the complexity of the cerebral cortex, and when grafted into the mouse brian they can integrate and recapitulate the neural circuits f the cortex, with direct relevance to brain repair. APPLICATION FIELDS • Modellling human brain development and diseases • Drug screen for diseases of cortical neurons (epilepsy, Alzheimer,autisme) • Toxicology screens on defined populations of nerve cells • Cell therapy for diseases of the cerebral cortex (stroke, epilepsy) ONGOING PROJECT(S) Modelling of human disases of brain development. Use of the technology in proof of concept experiments to cure cortical neuron loss by cell therapy replacement Université Libre de Bruxelles IRIBHM | 808 route de Lennik | 1070 Brussels | Belgium | http://dev.ulb.ac.be/pvdhlab Pierre Vanderhaeghen | Professor at ULB | +32 (0)2 555 42 86 | +32 (0)2 555 46 55 | [email protected] 17 LABORATORY R…G…N…RATIV… M…DICIN… ULB - IRIBHM (2) Our lab is studying the mechanisms that regulate stem cell functions during embryonic development, tissue homeostasis and cancer formation. In particular we are studying RESEARCH AXES / TECHNOLOGY Stem cells Stem Cells Heart Failure (HF) Role in cancer Mechanisms of differentiation • The cellular and molecular mechanisms regulating cell fate specification during embryonic development and tissue homeostasis. We are using embryonic stem cell to produce cardiovascular cells and dissect the mechanisms that regulate their specification and differentiation, which have important clinical implications. We are studying the mechanisms that control epithelial development and homeostasis including epidermis, mammary gland and prostate. • The role of adult stem cells during cancer initiation. For most cancers, the target cells of oncogenic mutations are unknown. We are determining whether epithelial stem cells are the initial target cells of oncogenic mutations during cancer formation. Using mouse genetic, we are also exploring the influence of the pre-existing self-renewing capacity of adult stem cells during cancer formation. • The role of cancer stem cells during cancer growth and relapse after therapy. Recent studies provide compelling evidence that certain leukemia and human solid tumors contain cells with high clonogenic potential, capable of reforming parental tumor upon transplantation, and which have been referred to as cancer stem cells. However, it remains unclear whether all cancers contain cancer stem cells and how do cancer stem cells contribute to the actual tumor growth. We are using different approaches combining cell isolation and transplantation as well as unbiased genetic approach to determine the contribution of cancer stem cells during epithelial cancer growth and relapse after therapy. APPLICATIONS FIELDS • Stem cells • Development • Cancer • Regenerative medicine Université Libre de Bruxelles IRIBHM | 808 route de Lennik | 1070 Brussels | Belgium | http://dev.ulb.ac.be/pvdhlab Cédric Blanpain | Professor at ULB | +32 (0)2 555 41 75 (41 90) | [email protected] 18 LABORATORY R…G…N…RATIV… M…DICIN… ULB - Laboratory of Bone Biochemistry and Metabolism Rheumatology and Physical Medicine Dept The laboratory and department have a solid scientific and technical expertise in bone métabolism, bone biology and bone cell therapy, and particularly in stem cells isolation, osteoblast culture, enzymatic testing, and gene expression analysis. In collaboration with Bone Therapeutics, they have set up in vitro tests and in vivo models to study the safety and efficacy of bone cell products. Stem cells Heart Failure (HF) Cell therapy Bone diseases Stem cells RESEARCH AXES/TECHNOLOGY Bone disease cell therapy APPLICATION FIELDS Bone disease including osteonecrosis, nonunion, fractures and osteoarthritis. ONGOING PROJECT(S) • Physiopathogeny of non-union: development of specific cell therapy product • Development of serum free media for cell therapy • Development of new treatment device for osteoarthritis Université Libre de Bruxelles Hôpital Erasme | Route de Lennik 808 | B 1070 Bruxelles | Belgium Pr Valérie Gangji | Head of Dept - +32 (0)2 555 36 50 | [email protected] Joanne Rasschaert | Director of Biochemistry dept | Faculty of Medicine | ULB [email protected] - +32 (0)2 555 63 07 19 LABORATORY R…G…N…RATIV… M…DICIN… ULg - Laboratory of Cell and Gene Therapy (CHU) Tissue bank Stem cells GMP cell Heart Failure production (HF) R&D Lymphocytes Dendritic cells Hematopoietic cells Mesenchymal stem cells Preosteoblasts The Laboratory of Cell and Gene Therapy (LTCG) at the University Hospital of Liège and the University de Liège boasts the largest experience in clinical and translational research in cell therapy in Belgium. It includes 3 tissue banks (hematopoietic cells, cord blood, nonhematopoietic cells) that have received Belgian AFMPS/FAGG, FACT-Netcord and JACIE accreditations, a R&D unit to transfer innovative cell technologies to the clinic, and an ATMP production lab producing et distributing cell products used in patients throughout Belgium in the context of approved clinical trials. RESEARCH AXES/TECHNOLOGY The major cell products prepared in the LTCG include: • Specifically selected or depleted populations of T lymphocytes (such as CD8-depleted T cells, regulatory T cells …) to be used in immunotherapy protocols in cancer or transplant patients; • WT1 mRNA-loaded dendritic cells to be used in tumor vaccination; • Mensenchymal stem cells (MSC) to be used as immunosuppressive therapy in hematopoietic as well as organ transplantation, and autoimmune diseases; • Marrow-derived MSC or pre-osteoblastic cells to be used for bone regeneration APPLICATION FIELDS The major therapeutic areas covered at the LTCG include: • Immunotherapy of cancer • Hematopoietic cell transplantation (HCT) and solid organ transplantation • Auto-immune diseases • Bone regeneration ONGOING PROJECT(S) Our major partners include: • The Center for Innovative Medicine (CIM), involved in collaborations with industrial partners for GMP product development and phase 1-2 clinical trials; • A network of Belgian academic hospitals involved in HCT; • International exchanges of hematopoietic cell products. Université de Liège LTCG (CHU de Liège) | CHU Sart-Tilman, 1 Av de l’Hôpital, | 4000 Liège | Belgium www.chu.ulg.ac.be/jcms/c_13333/therapie-cellulaire-et-genique Yves Beguin / Professor | +32 (0)4 366 72 01 | +32 (0)4 366 88 55 | [email protected] Etienne Baudoux / Director | +32 (0)4 366 83 94 | +32 (0)4 366 83 91 | [email protected] 20 LABORATORY R…G…N…RATIV… M…DICIN… ULg - Hematology Unit of the GIGA Research Institute Hematology Stem cells Transplantation Heart Failure Stem cells (HF) Cancer Hematopoietic cells Mesenchymal stem cells Regenerative medicine Immunotherapy The Hematology Unit of the GIGA-I3 research group is part of the larger GIGA Research Institute, a major multidisciplinary Research Center of the University of Liège focusing on genoproteomic approaches in the biomedical field.The Hematology unit specializes in the study of hematopoietic and other stem cells. This includes investigations of stem cell biology, purification and expansion, as well as the therapeutic use of these cells in the context of hematopoietic cell transplantation, immunotherapy of cancer and regenerative medicine. RESEARCH AXES/TECHNOLOGY The major research axes in our unit include: • Hematopoietic stem cells: biology, expansion, transplantation; • Investigation of immune function in patients; • Erythropoiesis and iron metabolism; • Mensenchymal stem cells (MSC): biology and therapeutic use; • Cellular immunotherapy of cancer, including multiple myeloma. APPLICATION FIELDS The major applications of our research in cell therapy are: • Hematopoietic cell transplantation (HCT) ; • Reconstitution of immune function after transplantation; • Cellular immunotherapy of cancer and graft-versus-host disease; • Regenerative medicine (liver, heart, bone). ONGOING PROJECT(S) Our major partners include: • Other units of the GIGA Research Institute ; • The Laboratory of Cell and Gene Therapy at the CHU of Liège ; • Numerous international partners involved in scientific collaborations ; • Private companies interested in cell products and our expertise in cell therapy. Université de Liège Hematology unit of the GIGA Research Institute | 1 Av de l’Hôpital, | 4000 Liège | Belgium www.giga.ulg.ac.be/jcms/prod_181503/en/haematology-lab Yves Beguin / Professor | +32 (0)4 366 72 01 | +32 (0)4 366 88 55 | [email protected] Frédéric Baron / PI | +32 (0)4 366 72 01 | +32 (0)4 366 88 55 | [email protected] 21 LABORATORY R…G…N…RATIV… M…DICIN… ULg - Laboratory of Thrombosis and Hemostasis, GIGA Research Institute Hemostasis Stem cells Coagulation Heart Failure Platelets (HF) Cancer Endothelial progenitor cells Marrow stromal cells Cancer stem cells Stem cell mobilization The Laboratory of Thrombosis and Hemostasis comprises scientists, clinical biologists and physicians active in basic and translational research in the field of hemorrhagic and thrombotic disorders. It is integrated in the GIGA Research Institute of the University of Liège. The research activities of the Laboratory of Thrombosis and Hemostasis are supervised by Cécile Oury and André Gothot who combine their expertise in platelets and stem cell biology, respectively. RESEARCH AXES/TECHNOLOGY The Laboratory of Thrombosis and Hemostasis focuses on the crosstalk between the hemostatic system and normal or cancer stem cells in hematological and cardiovascular diseases as well as in cancer. The Laboratory is equipped with a technological platform comprising cell culture and flow cytometry, coagulometers, analyzers dedicated to the study of platelet function, thrombinography and thromboelastometry instruments, murine models of thrombo-embolism by Doppler and intravital microscopy. APPLICATION FIELDS • Endothelial cell therapy in disseminated intravascular coagulation of sepsis • Role of platelet and myeloid cell purinergic receptors in bone marrow-derived stem cell mobilization • Contribution of platelets in the establishment of metastatic niches for colon cancer stem cells ONGOING PROJECT(S) Ongoing collaborations involve: • Several Departments of Liège University Hospital and GIGA-Research • Manufacturers of diagnostic reagents interested in biomarker stratification • Academic centers in UK, Netherlands and France, with expertise in platelet biology and coagulation Université de Liège Laboratory of Thrombosis and Hemostasis, GIGA Research Institute 1Av de l’Hôpital, 4000 Liège | Belgium | www.giga.ulg.ac.be Cécile Oury / PhD | +32 (0)4 366 24 87 | [email protected] André Gothot / MD, PhD | +32 (0)4 366 75 36 | [email protected] 22 LABORATORY R…G…N…RATIV… M…DICIN… ULg - Bone and Cartilage Research Unit Stem cells Osteoarthritis Heart Failure Biomarkers (HF) The Bone and Cartilage Research Unit is highly specialized in the pre-clinical and clinical investigation of joint diseases. Furthermore, BCRU has a great expertise in the diagnosis and follow-up of arthritic patients, mainly by the measurements of cartilage, muscles and bone turnover markers in serum, urine and synovial fluid. It has been serving, for more than 10 years, as a central laboratory facility, for these biomarkers in multicenter trials sponsored by pharmaceutical companies or governments. Based on patents, BCRU has founded two spin-off named “Artialis”(www.artilais.com) and “Synolyne”(www.synolyne. com). BCRU has initiated collaborative works with the most prestigious European and US universities on biomarkers and biomaterials research. RESEARCH AXES/TECHNOLOGY Cartilage Bone • Study of the role played by synovium inflammation, bone remodeling and chondrocyte hypertrophy in osteoarthritis development. • Research of new biomarkers for the diagnosis, prognosis and efficacy of drugs in joint disorders • Research of natural biomaterials for cell therapy and viscosupplementation treatments of osteoarthritic cartilage. APPLICATION FIELDS • Research and development of drugs, food supplments and medical devices • Joint disorders diagnosis • Tissue repair ONGOING PROJECT(S) • Study of the bone and cartilage neo-vascularization • Research of biomarkers for the monitoring of sarcopenia and intervertebral disk degeneration • Development of optimized biomaterials for cartilage repair induction. Université de Liège Prof Y Henrotin | Bone and Cartilage Research Unit, University of Liège, CHU Sart-Tilman, 4000 Liège – Belgium | [email protected] | +32 (0)4 366 25 16 | www.bcru.be 23 LABORATORY R…G…N…RATIV… M…DICIN… University of Namur (FUNDP) - Research Unit in Cell Biology Stem cells Proteomics Heart Failure (HF) Mitochondria Cell signaling Transcription factors The Research Unit in Cell Biology-Namur Research Institute for Life Sciences (URBC-NARILIS) of the University of Namur can rely on about 60 people, under the supervision of 6 professors or FNRS associated researchers to feed its research. The main research interest of URBC-NARILIS is to study how mammalian cells in culture respond to various stresses, ranging from atherogenic stress (Prof. M. Raes), metabolic stress (Prof. T. Arnould and P. Renard), hypoxia (Prof. C. Michiels) or aging/stress induced premature senescence (Dr. O. Toussaint and F. Chainiaux). Cell responses are analysed at the metabolic, transcriptomic and/or proteomic level, as well as with the whole panel of standard cell biology and biochemical assays. RESEARCH AXES/TECHNOLOGY • a complete proteomic platform, based on 2D-DIGE technology, working routinely with several mass spectrometers. This platform is largely used for research projects initiated by private companies as well as by other universities; • a “low oxygen” culture station, for culturing cells in more physiological conditions (typically 5% O2 instead of 21 % O2) which delay cell senescence; • a strong know-how in cell signaling, including in the study of transcription factor activation/regulation; • an expertise in the field of cell senescence and in toxicology (in vitro and in vivo) acquired during the Nanotoxico project funded by the Walloon Region. APPLICATIONS FIELDS Optimization of culture conditions for specific stem cellsCellular and biochemical characterisation of stem cells Cell-based in vitro modelling for toxicity screening on hepatic cells ONGOING PROJECT(S) • Study of mitochondrial biogenesis during the hepatogenic differentiation of human mesenchymal stem cells (A. Wanet PhD thesis, in close collaboration with Dr M. Najimi, PEDI, UCL) • Development of new cell-based in vitro models for ADME/toxicity screening, based on human adult progenitor/stem cells. VALOSTEM - Biowin convention n° 6221 FUNDP – University of Namur Rue de Bruxelles 61 | 5000 | Belgium | [email protected] www.fundp.ac.be/sciences/biologie/urbc/ 24 LABORATORY R…G…N…RATIV… M…DICIN… UCL - Cardiovascular Research Stem cells Stem cells for heart repair HeartforFailure Drugs cardiac (HF) regeneration Cardiac stem cells Epigenetics MicroRNA Nitric oxide, Immunogenicity Ischemic cardiac diseases Several Research Groups within the Pole of Pharmacology and Therapeutics, Pole of Cardiovascular Research and Pole of Experimental Surgery within the Institut de Recherche Expérimentale et Clinique (IREC) are involved in collaborative efforts subsidized by an Action de Recherche Concertée of the Communauté Wallonie-Bruxelles as well as the Politique Scientifique Fédérale, on the isolation and characterization of several stem cells (including cardiac stem cells or mesenchymal stem cells) of rodent, swine and human origin with the aim of identifying critical signalling mechanisms of proliferation and differentiation that can be modulated therapeutically for cardiac regeneration. Additionally, immunogenicity of allogeneic stem cell is studied both ex vivo and in vivo in a swine model of subacute ischemic cardiomyopathy. RESEARCH AXES / TECHNOLOGY • MACS isolation of cardiac stem cells from adult hearts • FACS selection and sorting based on specific antigens • Stem cells selection based on metabolic profiling • In vitro differentiation to cardiac lineages, including cardiac myocytes and phenotyping • In vivo implantation and stem cells tracing using isotopic labelling • Lineage specification by modulation of specific signalling pathways, e.g. Wnt/beta-catenin and nitric oxide synthase, or AMP-activated protein kinase • Stem cells transplantation in swine and humans • Tolerance to allogenic stem cell transplantation APPLICATIONS FIELDS • Foreseen therapeutic applications to ischemic cardiac diseases, myocardial infarction, heart failure • Drug screening to modulate cardiac regeneration based on in vitro differentiation assays ONGOING PROJECT(S) • Epigenetic mechanisms of cardiac stem cells lineage specification: modulation by specific drugs and nitric oxide • Modulation of Wnt/beta-catenin signalling for the control of proliferation/differentiation of cardiac stem cells • Identification of microRNA’s involved in stem cells re-programming • Modulation of AMPK signalling for the control of proliferation/differentiation of stem cells • National (ARC, PAI) and international (Fondation Leducq, FP7) partnerships Université catholique de Louvain / Institut de Recherche Expérimentale et Clinique (IREC) | B-1200 Brussels | Belgium Prof J-L Balligand / Head | Pole of Pharmacology and Therapeutics (IREC/FATH) +32 (0)2 764 52 60 | [email protected] Prof L. Bertrand | Pole of Cardiovascular Research (IREC/CARD) | +32 (0)2 764 55 52 | [email protected] Prof P. Gianello | Pole of Experimental Surgery (IREC/CHEX) | +32 (0)2 764 55 82 | [email protected] 8 LABORATORY R…G…N…RATIV… M…DICIN… UCL - Pediatric Hepatology and Liver Cell Therapy Liver stem cells Stem cells Regenerative Heart Failure medicine (HF) ATMP Orphan diseases Cell transplantation Phase I ATMP trials Urea cycle disorders Crigler Najjar This team from Université catholique de Louvain is internationally recognized for its research in liver regenerative medicine, from basic research on liver stem cells to translational and clinical studies.This pioneer center in hepatocyte and stem cell transplantation for orphan metabolic diseases is headed by Prof Etienne Sokal, founder of the spin-off Promethera Biosciences, and is an Orphanet expert center in pediatric liver diseases. RESEARCH AXES / TECHNOLOGY • Isolation of mature and progenitor human cells from liver, cord Wharton jelly and bone marrow. Isolation of liver mesenchymal progenitors, epithelial cells, stellate cells and endothelial cells. • Basic research on cell-cell interaction and hepatocyte differentiation. • Cryopreservation • Pre-clinical research on stem cell large scale expansion, biodistribution, pro-coagulant activity, animal models of stem cell transplantation. • Human cell models for viral replication. • Accredited tissue bank (hepatocyte and liver stem cells), human hepatocyte and ATMP transplantation. • Phase one clinical trials with liver progenitor cells in urea cycle disorders and Crigler Najjar. APPLICATIONS FIELDS • Treatment of acquired and congenital liver diseases. • Treatment of liver fibrosis, liver immune disorders, liver based inborn errors of metablism such as urea cycle defects, Crigler Najjar syndrome, phenylketonuria, organic aciduria, Refsum disease and clotting factor deficiencies. • In vitro testing of new drugs: ADME tox studies, viral cycle platform. ONGOING PROJECT(S) Differentiation of liver stem cells in vitro, cell-cell interactions in co-culture systems, in vivo cell tracking, biodistribution, pro-coagulant activity of stem cells, immunogenicity and diagnosis of rejection, animal models of fibrosis. ADME tox studies using non transformed human liver cell lines, human cell models of HBV, HCV, CMV viral cycle. Phase I/II clinical studies in urea cycle diseases and Criggler Najjar syndrome. Public Private Partnership projects. Université catholique de Louvain | Avenue Hippocrate 10 bte B2.2543 | B-1200 Brussels (Woluwe) | Belgium Etienne SOKAL | Prof. Ordinaire at Université Catholique de Louvain | +32 (0)2 764 13 86 | +32 (0)2 764 89 09 [email protected] 9 RELATED ACTIVITIES Summary table TYPE OF ORGANIZATION PAGE BIOMATERIALS KitoZyme Company 27 Synolyne Company 27 UCL – CRIBIO Research Laboratory 28 UMons – CIRMAP Research Laboratory 28 ULg – Centre Interfacultaire des Biomatériaux Research Laboratory 29 ULg – Biomechanics Research Unit Research Laboratory 29 Research Laboratory 30 CELL CULTURE AND SUPPORT EXPERTISE UCL – Hepato-Gastroentology Liver and Pancreas Development UCL – Genetics Research Laboratory 31 ULB – Laboratory of Clinical Cell Therapy Research Laboratory 32 UMons – Laboratory of Human Biology and Toxicology Research Laboratory 32 Ulg – Genetics (CHU Liège) Research Laboratory 33 ULg – Laboratory of …xperimental Pathology Research Laboratory 33 sCINNAMIC – Centre of Medical Innovation (CIM) Company 34 CMMI Infrastructure / Core facilities 34 GIGA – Tech Platforms Infrastructure / Core facilities 35 PLATFORMS UNILAB – Lg Hematology Infrastructure / Core facilities 35 UCL – Imaging Infrastructure / Core facilities 36 Training Centre 37 TRAINING Biopark Formation RELATED ACTIVITIES REGENERATIVE MEDICINE REGENERATIVE MEDICINE COMPANIES R…G…N…RATIV… M…DICIN… R…LAT…D ACTIVITI…S BIOMATERIALS BIOMATERIALS KitoZyme SYNOLYNE KitoZyme is a manufacturer of biopolymers from renewable, non-GMO vegetable sources and a full-service provider of medical devices. One of KitoZyme’s missions is to develop a new generation of cell scaffolds for cell culture/therapy and regenerative medicine. These scaffolds rely on KiOmedine® ultra-pure chitosan, a natural biopolymer with a unique combination of properties, that is endotoxin-free, non animal-derived and manufactured following ICH Q7 GMP guidelines. Thanks to its highly qualified R&D team, KitoZyme has accumulated extensive expertise in formulation, processing, analytical development and scaling-up performances to help its partners address challenging therapeutic needs. KitoZyme is ISO-9001:2008 and ISO 13485 certified and complies with GMP and HACCP. RESEARCH AXES/TECHNOLOGY/SERVICES KitoZyme hydrogel platform is a family of hydrogels/sealants derived from chitosan and chitosan derivatives, some of which are liquid at room temperature and spontaneously turns to gel at body temperature. They offer beneficial properties to address unsatisfied markets (bone and cartilage repair, cardiovascular, aesthetic surgery, biosurgery, etc). Chitosan-based hydrogel offers 9 key features crucial for in vitro cell culture, in vivo animal studies and beyond: • Well–defined composition • Customizable for a fine tuning of the gel properties • Liquid at room T° for injection through small size needles (19 G) • Formation at physiological pH, osmolarity and temperature • Bioresorbable with time leaving behind the newly formed tissue. • Biocompatible: spontaneous gel formation (without catalyst) using anionic crosslinker; providing MSC cells with the right environment to survive, migrate and proliferate. • Bio/mucoadesive • Able to sequester and slowly release drugs or biomolecules (growth factors, etc). • Suitable for implantation/injection: gels made according to GMP. RESEARCH AXES / TEHNOLOGY / SERVICES Chitosan, injectable hydrogels, tissue engineering, cell therapy, cell/drug delivery, regenerative medicine CONTACTS KitoZyme | Parc Industriel des Hauts Sarts – zone 2 rue Haute Claire 4 | 4040 herstal | Belgium +32 (0)4 259 85 00 | [email protected] 26 Synolyne is a spin-off of the University of Liège and a spin-out of Kitozyme sa. This company is specialized in the development and commercialization of patented medical devices for the viscosupplementation of arthritic joint and the cell therapy of cartilage lesion. The product (Arthrovisc®) is a biphasic chitosan hydrogel with mechanical and biological properties protecting cartilage and promoting cartilage matrix repair . RESEARCH AXES/TECHNOLOGY/SERVICES • Bio-optimized hydrogel for intra-articular treatment of joint diseases • Bio-optimized matrix for cell therapy • Natural micro-carriers for drugs and nutraceuticals delivery KEYWORDS Arthritis, joint, Cartilage, matrix, viscosupplementation, chitosan, cell therapy. CONTACTS SYNOLYNE SA | GIGA Tower, Level 3 | CHU Sart-Tilman Ave nue de l’hôpital 11 | 4000 Liège | Belgique LABORATORIES R…G…N…RATIV… M…DICIN… R…LAT…D ACTIVITI…S BIOMATERIALS BIOMATERIALS UCL - CRIBIO UMons - CIRMAP The Center for Research and Engineering on Biomaterials (CRIBIO) at UCL (Université catholique de Louvain) gathers experts from more than 20 research teams involved in research projects centered on biomaterials. CRIBIO aims at developing a pluridisciplinary approach, from the lab to the patient. Its members are active in a large number of fields, including regenerative medicine. RESEARCH AXES/TECHNOLOGY/SERVICES Several members of the CRIBIO are conducting research projects on cell culture systems, tissue engineering, bioartificial organs, and regenerative medicine. Cutting-edge technologies, such as the design and elaboration of biointerfaces, the physico-chemical characterization and functionalization of materials or the synthesis of bio-active molecules are mastered by the CRIBIO experts and tested from in vitro models to clinical studies. KEYWORDS Biomaterials, tissue engineering, stem cells, cell culture, bio-interfaces, hydrogels, scaffolds, cryopreservation, polymers CONTACTS Université catholique de Louvain CRIBIO Sophie Demoustier and Christine Dupont Professors and spokeswomen Croix du Sud | 1 bte L7.04.02 B-1348 Louvain-la-Neuve | Belgium Gaëtane Leloup Professors and spokeswomen Avenue Hippocrate 10 bte B2.5721 B-1200 Brussels (Woluwe) Belgium [email protected] | www.uclouvain/cribio The Center of Innovation and Research in Materials and Polymers (CIRMAP), and more particularly its Laboratory of Polymeric and Composite Materials, takes advantage of its wide expertise in control polymerization techniques and macromolecular engineering to develop well-defined cross-linked polymer networks presenting good control over macromolecular parameters and predictable physicochemical properties. CIRMAP is involved in the synthesis of hydrogels (monolithic, injectable, nano-size) for 10 years with in scope the development of new bioresorbable scaffolds for cell development in the frame of regenerative medicine or for controlled drug delivery. RESEARCH AXES/TECHNOLOGY/SERVICES CIRMAP objectives are oriented towards a fine control/tuning over the polymer synthesis, and to an in-depth characterization of the resulting material properties, aiming at targeting new applications in industrial domains as biomedical and pharmaceutical areas. CIRMAP is particularly involved in the use and in the understanding of some key controlled polymerization techniques such as metal-free ring-opening polymerization and controlled radical polymerization (ATRP, RAFT) as well as in Click chemistry reactions, allowing the preparation of tailor-made materials. These domains can be covered owing to the remarkable instrumental park available at CIRMAP, in terms of synthesis and characterization of the polymeric materials. KEYWORDS Injectable hydrogels, hydrogel films, bioresorbable, thermo-responsive properties, biocompatibility. CONTACTS University of Mons (UMONS) CIRMAP 20 Place du Parc | 7000 Mons | Belgium Dr. Mespouille Laetitia |[email protected] http://morris.umons.ac.be/CIRMAP 27 LABORATORIES R…G…N…RATIV… M…DICIN… R…LAT…D ACTIVITI…S BIOMATERIALS BIOMATERIALS ULg - Centre Interfacultaire des Biomatériaux ULg - Biomechanics Research Unit CEIB is composed of 13 different laboratories/services with 31 representative members. Their disciplines cover the fields of material synthesis and characterisation (polymer, metal, ceramic, biopolymers, dispersed materials (micro- nanoparticles, …), surface coating, biomaterial testing (in vitro, in vivo) and of their preclinical and clinical investigations. Specific expertises of the CEIB in the area of biomaterial concern: synthetic polymer engineering, in particular for the production of biodegradable biocompatible polymers (PLA, PCL, PLGA), including degradable amphiphilic gels designed for tissue engineering. CEIB provides analytical services for the medical and pharmaceutical industries, see www.ulg.ac.be/ceib The Biomechanics Research Unit was established in 2009 within the aerospace and mechanical engineering department of the university of Liège. The research unit, led by Prof. Liesbet Geris, consists of a mix of PhD students and postdocs with backgrounds varying from applied mathematics over mechanical and material engineering to developmental biology. The experimental part of the unit’s research work is based in the laboratories of Prometheus, the KU Leuven R&D division of Skeletal Tissue Engineering of which Prof. Geris is the scientific coordinator. The research unit is supported through university, regional and European funding. Prof. Geris recently obtained an ERC starting grant to further investigate in silico biomimetic process design in regenerative medicine. RESEARCH AXES/TECHNOLOGY/SERVICES RESEARCH AXES/TECHNOLOGY/SERVICES •Optimisation of biomaterial composite fiber-hydrogel-cell to promote bone reconstruction. This project allows us now to evaluate a new biodegradable implant in clinical phase. • Biomaterials loaded with thrombinomimetic peptides optimised to promote cicatrisation and reparation of tissues. • Hemocompatibility study of new polycations tailored to modify the surface of biomaterials designed for cardiovascular surgery. • Nanoscale Functionalities for Targeted Drug Delivery of biopharmaceutics • Sustainable Production of Advanced Functional Materials for medical application. • Fluorescent labeling of polymers to follow their biodistribution The Biomechanics Research Unit focusses on the use of mathematical models to elucidate developmental processes and the application of these models to improve the design of bone regenerative processes which should lead to enhanced quality and quantity of the final product. We have implemented a suite of model systems ranging from mechanistic models (hypothesis-based) over gene regulatory network models to empirical models (data-driven), targeting processes at the intracellular over the cellular up to the tissue level. Mechanistic models are used as in silico tools to design new therapeutic strategies and experiments, e.g. to investigate the dosage and timing of cell and growth factor delivery in non-unions and large bone defects. Empirical models are used to identify, in large data sets, those in vitro parameters (biological, biomaterial, environmental) that are critical for the in vivo outcome, e.g. to steer the development of novel biomaterials. KEYWORDS Biodegradable polymers | Blood compatible | Polyelectrolyte Hydrogel | Surface | Functionalisation | Degradable KEYWORDS In silico medicine, developmental engineering, materiomics, process design, biomimetics, bone CONTACTS Université de Liège CEIB | Chemistry Institute, B6c | B-4000 Liege | Belgium [email protected] | www.ceib.ulg.ac.be 28 CONTACTS Université de Liège Biomechanics Research Unit Chemin des Chevreuils 1 B52/3 | 4000 Liège http://www.biomech.ulg.ac.be Liesbet Geris, Research Unit Leader T. +32 (0)4 366 95 87 | F. +32 (0)4 366 95 05 [email protected] LABORATORIES R…G…N…RATIV… M…DICIN… R…LAT…D ACTIVITI…S CELL CULTURE AND SUPPORT EXPERTISE UCL - Hepato-gastroenterology Liver & Pancreas Development Regenerative therapy of liver disease depends on the availability of large amounts of high quality hepatocytes. Producing such cells in vitro, designing appropriate administration protocols and obtaining efficient engraftment in the recipient organ requires extensive knowledge on how hepatocyte differentiate, proliferate and interact with their environment. Research at the "Hepato-Gastroenterology" and "Liver and Pancreas Development" groups focuses on hepatocyte biology in normal liver development and in adult diseased liver. Identification of basic molecular mechanisms translates into improved protocols for cell therapy of liver disease, as well as on identification of targets to stimulate functional regeneration from native cells. RESEARCH AXES/TECHNOLOGY/SERVICES Using molecular and developmental biology approaches, combined with imaging (including confocal and multiphoton microscopy) and mouse transgene technology, the research groups identify intercellular signaling mechanisms (diffusible and extracellular matrix-related signaling) and intracellular gene regulators (transcriptional regulators and microRNAs) that modulate hepatocyte differentiation in normal development and in regenerating liver. The "Hepato-Gastroenterology" and "Liver and Pancreas Development" research groups provide the research community with hepatocyte differentiation assays, with new signaling effectors and gene regulators that modulate hepatocyte differentiation or benchmark the quality of in vitro produced hepatocytes, and with animal models for liver regeneration and cell therapy. KEYWORDS Liver, hepatocyte, differentiation, regeneration CONTACTS Université catholique de Louvain GAEN | Avenue Mounier 53/B1.52.01 | B-1200 Brussels (Woluwe) | Belgium | [email protected] www.uclouvain.be/398887.html Université catholique de Louvain LPAD | Avenue Hippocrate 75/B1.75.03 | B-1200 Brussels (Woluwe) | Belgium | [email protected] www.deduveinstitute.be/liver_and_pancreas_development.php 29 LABORATORIES R…G…N…RATIV… M…DICIN… R…LAT…D ACTIVITI…S CELL CULTURE AND SUPPORT EXPERTISE UCL - Genetics Several complementary UCL clinical and research teams offer their expertise in Genetics. These teams are structured as a Center, which includes both clinical and laboratory activities (the Center for Human Genetics), as platforms, such as the Microarray Platform UCL in de Duve Institute and the Center for Applied Molecular Technologies (CTMA), or as classical research groups. State-of-the-art technologies routinely performed in these laboratories provide strong support to research in the field of cell therapy. RESEARCH AXES/TECHNOLOGY/SERVICES • Genetic stability studies by karyotyping, FISH, and molecular karyotyping, especially on cultured cells, and expert interpretation (1) • UCL platforms of high-throughput sequencing (NGS) of exomes, genomes, RNAseq etc, as well as high-density microarrays, with expertise in the biostatistical analyses and interpretation (2) • Development and validation of molecular and genetic tools and methods including low and high density microarrays and high-throughput sequencing, related biostatistics analyses, teratogenicity, measure of p53 functional deficiency (3) • Genetic and epigenetic alterations of the genome, DNA methylation and histone modification analyses, various telomere-related analyses (4) KEYWORDS Genetics, epigenetics, FISH, karyotyping, next generation sequencing (NGS), microarrays, genetic stability, telomeres 30 CONTACTS UCL Center for Human genetics Miikka Vikkula and Hélène Antoine-Poirel Av. Mounier, F | B-1200 Brussels (Woluwe) | Belgium +32 (0)2 764 67 81 | [email protected] [email protected] GEHU Human Molecular Genetics Miikka Vikkula and Mustapha Amyere Av. Hippocrate 75 bte B1.75.02 B-1200 Brussels (Woluwe) | Belgium +32 (0)2 764 74 96 | [email protected] [email protected] Center for Applied Molecular Technologies Jean-Luc Gala Clos Chapelle-aux-champs 30 bte B1.30.24 B-1200 Brussels (Woluwe) | Belgium +32 (0)2 764 31 65 | [email protected] www.ctma.be GEPI Genetics and Epigenetics Anabelle Decottignies and Charles De Smet Av. Hippocrate 75 bte B1.75.02 | B-1200 Brussels (Woluwe) Belgium | [email protected] [email protected] http://www.deduveinstitute.be/genetic_epigenetic.php LABORATORIES R…G…N…RATIV… M…DICIN… R…LAT…D ACTIVITI…S CELL CULTURE AND SUPPORT EXPERTISE CELL CULTURE AND SUPPORT EXPERTISE ULB - Laboratory of Clinical Cell Therapy UMons - Human Biology & Toxicology Laboratory Human MSC, found in many adult and fœtal tissues, hold the potential to revolutionize clinical approaches promoting tissue regeneration. MSC also possess immunomodulatory and immunosuppressive properties which could improve acceptance of allogeneic cells used for regenerative therapy. MSC from various origins exhibit different features. The study of biological properties of MSC including immunoregulatory characteristics, differentiation capacity and trophic potential is relevant in the context of MSC-based therapies. Since MSC are tightly regulated by their microenvironment, microbial products or inflammation can also influence their fate. RESEARCH AXES/TECHNOLOGY/SERVICES • Procedures to isolate MSC from BM and alternative sources (adipose tissue, umbilical cord, skine) • Functional characterization of MSC isolated from different tissue sources: differentiation potential, immunomodulation, migration and trophic factor secretion • Influence of the microenvironment on MSC functions (inflammation, infection, hypoxia) • Role of Toll-like receptor triggering in MSC activities • Development of FBS-free medium for clinical applications • Generation and expansion of regulatory T cells by MSC according to their origin • Cell culture rooms, cell laboratory, equipments for the study of cellular and molecular biology (real time PCR, flow cytometer,...) The Human Biology & Toxicology Laboratory is part of the School of Medicine & Pharmacy at the University of Mons. The laboratory develops research activities in the field of prospective toxicology. In particular, the laboratory is recognized for its expertise in metabonomics. RESEARCH AXES/TECHNOLOGY/SERVICES The laboratory conducts research activities in the field of predictive toxicology, primarily involving the use of metabonomics in various in vitro and in vivo animal models, as well as in clinical studies. The metabonomic approach is based on the spectroscopic (NMR and MS) analysis of biofluids and tissues combined to multivariate data analysis to obtain metabolic signatures characteristic of drug-induced adverse effects or pathologies. Biomarkers can be next identified from such signatures. The main research projects are mitochondrial toxicities, protein-adducts, cancers, nephropathies, and pre-eclampsia. Services include preclinical toxicological assessment, analysis of metabolic disturbances caused by drugs or diseases, and identification of toxicity marker metabolite for early detection of drug candidates which will cause undesirable effects. Analysis of metabolic disturbances caused by drug, disease, or toxic substance. KEYWORDS Toxicology, metabonomics, biomarkers, NMR KEYWORDS CONTACTS Mesenchymal stromal cells, immunomodulation, toll-like receptor, inflammation, differentiation UMons Laboratory of Human Biology & Toxicology Avenue du Champ de Mars, 8 | 7000 Mons | Belgium http://www.umons.ac.be CONTACTS Université Libre de Bruxelles Laboratory of Clinical Cell Therapy | ULB721 Campus Erasme | Bâtiment de Transfusion | Etage 1 808, Route de Lennik | 1070 Bruxelles | Belgique [email protected] | [email protected] 31 LABORATORIES R…G…N…RATIV… M…DICIN… R…LAT…D ACTIVITI…S CELL CULTURE AND SUPPORT EXPERTISE CELL CULTURE AND SUPPORT EXPERTISE ULg - Genetics (CHU Liège) ULg - Laboratory of Experimental Pathology The department of Human Genetics is part of Unilab-Lg, which comprises laboratories of three major disciplines, i.e., Clinical Biology, Genetics and Pathology, at Liège University Hospital. Unilab-Lg employs more than 300 technicians, scientists, pharmacists or physicians. A common quality assurance platform accredited by BELAC ensures that all steps involved in laboratory data acquisition are carefully controlled. State-of-the-art technical facilities are shared among all disciplines and are available for routine diagnosi TECHNOLOGY SERVICES • Genetic and chromosomal characterization of stem cells, regular activity for the Cell Therapy Laboratory. Demonstration of the chromosomal stability/instability of stem cells. • DNA sequencing (including NGS) • Diagnosis and patient sélection on genetic basis RESEARCH AXES The department of Human Genetics is involved in the genetic characterization of various human diseases including cancers and hereditary conditions. It has access to specific up to date facilities and platforms for genetic and molecular characterization of human or animal samples. The Laboratory of Experimental Pathology (LEP) has extensive expertise in the field of oncology and tumor immunology as evidenced by its number of publications this subject. In addition, the LEP is integrated into the GIGA-Cancer and GIGA-I3 (infection, immunity and inflammation) units of the GIGA-R (http://www.giga.ulg.ac.be) and works in partnership with GIGA technology platforms (imaging and cytometry, immunohistochemistry). The equipment and technical expertise (cell culture cell isolation (CD34+, NK, DC), functional testing, molecular biology, ...) necessary to optimize culture conditions or cell differentiation but also for immunophenotypic analysis are available in the LEP. RESEARCH AXES/TECHNOLOGY/SERVICES • Immunological characterization of cells: • Phenotype: flow cytometry and immunostaining (in association with imaging and immunohistology platforms) • Functional tests: production of cytokines (ELISA, Intracytoplasmic labeling), proliferation and cytotoxicity assays • Cell differentiation (DC, pDC, macrophages) • Organotypic cultures and cultures in microgravity KEYWORDS Phenotype, immunolabelling, culture conditions, cell differentiation, organotypic cultures KEYWORDS Genetics – Genomics – Chromosomes – DNA sequnecing CONTACTS Université de Liège LEP | Tour de Pathologie +4, CHU Sart Tilman 4000 Liège | Belgium Pr. Ph. Delvenne | [email protected] Dr Jacobs | [email protected] Dr P. Hubert | [email protected] CONTACTS Université de Liège Genetics | CHU B35 | 4000 Liège [email protected] 32 COMPANIES R…G…N…RATIV… M…DICIN… R…LAT…D ACTIVITI…S PLATFORMS PLATFORMS sCINNAMIC - Centre for Innovation in Medicine (CIM) CMMI sCINNAMIC (S.A. Centre for Innovation in Medicine) is an initiative from the Walloon government to promote biomedical translational research in this booming region of Belgium. Its aim is to stimulate biomedical innovation in Wallonia and internationally by providing those services needed to accelerate projects with high industrial potential. It will boost the environment linking three key innovation partners: industry, clinicians and basic researchers. Through the identification, build-up and coordination of translational projects we will provide a better future for Wallonia, for its citizens and for its industry. The Center for Microscopy and Molecular Imaging (CMMI) was created by UMONS and ULB, thanks to the financial support of the European Union and Wallonia (FEDER Convergence Program). The CMMI provides an integrated and efficient preclinical biomedical imaging platform composed of 10 research facilities having state-of-the-art equipment and offering cutting-edge technologies for electron microscopy, holography microscopy, fluorescence microscopy, flow cytometry, automation and quantitative cytometry, immunohistochemistry, autoradiography and in vivo imaging (optical, MRI and nuclear). RESEARCH AXES/TECHNOLOGY/SERVICES RESEARCH AXES/TECHNOLOGY/SERVICES A sCINNAMIC proof of concept was launched in Liege given the unique situation offered by the synergy of the University of Liege, the University Hospital (CHU), its life sciences research center (GIGA), and biotech companies all found in a single location. Banking on the expertise of the Laboratory of Cell & Gene Therapy (LTCG), one of its major pilot projects is in regenerative medicine. sCINNAMIC will soon offer hosting in GMP cell and gene therapy laboratory facilities. It will flexibly be complemented with services ranging from regulatory to full logistical support. The focus will be on method development including validation and up-scaling, and on ATMP production for preclinical and clinical trials (phases I and II). The structure has a proven track record with clients such as Cardio3 BioSciences. • Preclinical imaging from cells to rodents (rats and mice) • Diagnostic, pronostic and theragnostic biomarkers studies. • Novel drugs evaluation studies • Development and validation of contrast agents • Monitoring of molecular and physiological processes • Molecular Imaging of Stem Cells: monitoring of cell viability, proliferation, differentiation, biodistribution, tumorigenicity, and immunogenicity. • Cell culture control using holographic microscopy (cell fusion,..) • Ultrastructure analyses by TEM and SEM • Functional studies, phenotyping, cell cycle, apoptosis/nuclear damage, transcription factor, nuclear translocation by Imaging Flow Cytometry • General and specific training modules in imaging techniques KEYWORDS Translational research, cell production, lab rental, consulting, project management and coordination KEYWORDS Preclinical Imaging, SEM, TEM, holography, flow cytometry, automation, immunohistochemistry, autoradiography, in vivo CONTACTS sCINNAMIC / CHU de Liège Domaine Universitaire du Sart Tilman – B 34 | B-4000 Liège Belgium | [email protected] | www.scinnamic.be Stephane Berghmans, CEO | [email protected] +32 (0)471 071 038 33 CONTACTS Center for Microscopy and Molecular Imaging (CMMI) rue Adrienne Bolland, 8 | B-6041 Gosselies | Belgium [email protected] | www.cmmi.be LABORATORIES R…G…N…RATIV… M…DICIN… R…LAT…D ACTIVITI…S PLATFORMS PLATFORMS GIGA Tech Platforms Unilab Lg - Hematology From the organism to molecules. GIGA technology platforms gather up-to-date technologies managed by experts who are fully dedicated to the Platforms. All services and equipments are open to academic researchers and private sector contributing to speeding up biomedical research, including regenerative medicine. Platforms are either accredited (AFMPS for proteomics) or under quality control (GMP-like platforms for SPF Mouse and Zebrafish) guaranteeing its customers high quality services. RESEARCH AXES/TECHNOLOGY/SERVICES GIGA-Technology Platforms provide services ranging from to the use of animal experimental models (Zebrafish or mouse) to the analysis of the molecule (DNA or protein). There are several mouse facilities under GLP-like requirements dedicated to different purposes: A1, A2 and A3 biosafety levels; conventional and SPF health status (following FELASA guidelines). On the other hand, the Zebrafish animal facitily is ideal for both basic research studies (embryonic development, signal transduction pathway, ...) and for applied research (screening of new molecules, toxicity tests,…). The analysis of tissues can be done combining automated immunohistochemistry (Ventana XT, slide scanning) and Imaging platforms (eg.: Nikon A1R, Leica SP5 AOBS). The cells can be sorted by Flow cytometry (eg.: BD FACSCanto II) or screened using a High Content (BD Pathway). The proteins can be identified using mass spectrometry (eg.: Q-exactive MS) on the Proteomic platform under AFMPS agreement. Even nucleic acids can be deeply sequenced using Next Generation sequencers (Illumina, Roche and Life Tech) and thouroughly analyzed by our Bio-IT team. The Department of Laboratory Hematology and Immuno-Hematology is part of Unilab-Lg, which comprises laboratories of three major disciplines, i.e., Clinical Biology, Genetics and Pathology, at Liège University Hospital. Unilab-Lg employs more than 300 technicians, scientists, pharmacists or physicians. A common quality assurance platform accredited by BELAC ensures that all steps involved in laboratory data acquisition are carefully controlled. State-of-the-art technical facilities are shared among all disciplines and are available for routine diagnosis, assay development as well as translational and clinical research. RESEARCH AXES/TECHNOLOGY/SERVICES The laboratory has a strong expertise in biological characterization of cellular products, such as hematopoietic and mesenchymal stem cells, dendritic cells, lymphocyte subpopulations and osteoprogenitors. The procedures involve immunophenotyping by flow cytometry, cytokine secretion assays and clonogenic cell cultures. The laboratory also perfoms histocompatibility (HLA) typings for the matching of patient and organ or cell transplants and is in charge of the hematological and immunological monitoring of transplanted patients. With its Immuno-Hematology and Transfusion unit, the laboratory provides cell support of erythrocytes and platelets for recipients of hematopoietic stem cell transplants. KEYWORDS Immunophenotyping, cell culture, histocompatibility, transfusion, patient monitoring, quality assurance. KEYWORDS CONTACTS Genomics, proteomics, SPF Mouse facility, Zebrafish, Flow cytometry, Imaging, Immunohistochemistry Université de Liège (CHU) Unilab-Lg | 13, avenue de l’hopital B-4000 | Liège | Belgium [email protected]. André Gothot / MD / PhD | T. +32 (0)4 366 75 36 F. +32 (0)4 366 73 94 | [email protected]. CONTACTS Université de Liège (ULg) GIGA Tech Platforms | Avenue de l’Hopital 1 B34 4000 Liège | Belgium | [email protected] www.giga.ulg.ac.be 34 LABORATORIES R…G…N…RATIV… M…DICIN… R…LAT…D ACTIVITI…S PLATFORMS UCL - Imaging The imaging platforms at UCL (Université catholique de Louvain) are complementary and, thanks to cutting-edge equipments and knowhow, are offering their cross-sectional expertise to the research in cell therapy. RESEARCH AXES/TECHNOLOGY/SERVICES • Structured illumination fluorescence microscopy, in vivo bioluminescence and Doppler imaging (1) • Vital fluorescence imaging of cells and organs, high throughput /high resolution confocal microscopy, multiphoton microscopy, transmission and scanning electron microscopy (2) • In vivo imaging by Nuclear Magnetic Resonance (RMN- 11.7 Tesla) of tissue remodeling after injection of stem cells, oxidative stress and NO measurement by spin-trapping ESR (3) • In vivo imaging by Positron Emission Tomography (PET) and Simple Photon Emission Completed Tomography (SPECT) of genetically modified stem cells (4) • Laser microdissection, histology and immunohistochemistry platforms, laser capture microscopy (5) KEYWORDS Imaging, PET, SPECT, NMR, bioluminescence, Doppler, Confocal, Multiphoton microscopy, Tissue remodeling, Homing 35 CONTACTS Université catholique de Louvain IREC imaging platform Avenue Mounier 53 bte B1.53.09 B-1200 Brussels (Woluwe) | Belgium [email protected] http://sites.uclouvain.be/freeplane/IREC-Imaging-Platform.html DDUV Imaging platform Avenue Hippocrate 75 bte B1.75.02 B-1200 Brussels (Woluwe) | Belgium [email protected] www.icp.ucl.ac.be/microscopy Magnetic resonance imaging platform Avenue Mounier 73 bte B1.73.08 B-1200 Brussels (Woluwe) | Belgium [email protected] http://www.uclouvain.be/en-rema.html Center of Molecular imaging, Radiotherapy and Oncology (MIRO) Avenue Hippocrate 55 bte B1.55.02 B-1200 Brussles (Woluwe) | Belgium [email protected] www.uclouvain.be/398881.html Anatomopathology Avenue Hippocrate 10 bte2 B-1200 Brussels (Woluwe) | Belgium [email protected] ORGANISATION R…G…N…RATIV… M…DICIN… R…LAT…D ACTIVITI…S TRAINING BIOPARK FORMATION BIOPARK Formation is the Red Biotech & Biomed Training Centre on the BIOPARK industrial and academic campus.Its mission is to develop innovative training sessions to support the excellence of academic and industrial R&D in the field of Life Sciences. The Centre targets 3 audiences: (i) scientists, technicians and managers wishing to keep their technical and managerial skills up to date; (ii) higher education teachers who need to teach qualified students while meeting the needs of industry; (iii) job seekers who represent a reserve of potential future qualified staff. RESEARCH AXES/TECHNOLOGY/SERVICES BIOPARK Formation supports the development of innovative advanced therapies based on cell culture by proposing specific technical, scientific and managerial training sessions approved by the Health competitiveness cluster BioWin, eg: • Various technological intensive hands-on trainings of short duration; • BIOCEL: a set of training modules oriented towards cell culture and cell therapy in collaboration with Cefochim. Customeroriented, BIOCEL has several courses and practical training modules, each adapted to a certain profile or function (R&D lab, QC or production biotechnologists, managers and teachers); • STRATEGIO: an intensive and comprehensive Strategic Management Programme for Life Sciences Industry Executives, in collaboration with the Solvay Brussels School. KEYWORDS Training, education, technical skills, managerial skills, executive education, cell biology, cell therapy, strategic management CONTACTS Université Libre de Bruxelles BIOPARK Formation | B-6041 Gosselies | Belgium [email protected] http://www.biopark.be/bioparkformation 36 COMPANY R…G…N…RATIV… M…DICIN… The LIEU network brings together the Knowledge Transfer Offices (KTOs) from Universities and Higher Education Schools of the Wallonia-Brussels Federation in Belgium, with the aim of optimizing their scientific and technological potential in favor of innovation and regional development through a collective approach. Université Libre de Bruxelles Patrick Di Stefano, PhD Stem cells Technology Transfer Office Heart Failure Head of the Life Sciences Working Group (HF) Rue des Prof. Jeener et Brachet 12 6041 Gosselies | +32 (0)71 37 86 56 [email protected] Université of Namur (FUNDP) Facultés Universitaires Notre-Dame de la Paix Fabienne Roussel, PhD Technology Transfer Office Rue de Bruxelles 61 5000 Namur | +32 (0)81 72 57 07 [email protected] MORE SPECIFICALLY, THE MISSIONS OF THE LIEU NETWORK ARE • To strengthen and improve the partnership activities of the universities with their socioeconomic environment, with the prospect of a regional development; • To promote collaborations between the Knowledge Transfer Offices of the universities; • To promote vocational orientation of intermediation and knowledge transfer through training programs, the sharing of good practices and the development of common tools; • To play a part in the international promotion of the scientific and technological potential of the universities; • To take part in the European and international interface and technology transfer networks. The LIEU network has set up Thematic Work Groups made up of KT officers from member institutions with the aim of developing common activities in various fields: thematic knowledge transfer, communication and technological animation, legal aspects, international relations, quality management etc. Within that framework, it is the task of the "Life Sciences Work Group" to carry out the specific missions of the LIEU network in relation with the Life Sciences field: it acts as the entry point of the network. Association des Directions des Instituts Supérieurs Industriels Francophone Christine Deom, MSc Technology Transfer Office Rue des Pieds d’Alouette 39 | 5100 Naninne +32 (0)81 41 38 12 | [email protected] Université Catholique de Louvain Marlène Dubuisson, PhD Technology Transfer Office Place de l’Université 1 1348 Louvain-la-Neuve | +32 (0)10 47 25 42 [email protected] Université de Mons Marlène Genlain, PhD Technology Transfer Office Rue de Houdain 9 | 7000 Mons +32 (0)65 37 47 78 | [email protected] 1 Université de Liège Sabine Olivier, PhD Technology Transfer Office Avenue Pré Aily 4 | 4031 Angleur +32 (0)4 349 85 09 | [email protected] Design | www.hoet-heot.eu The southern French-speaking part of Belgium is ideally located between Northern Europe and Southern Europe. Belgium is also neighbor to France, Germany, Luxembourg and the Netherlands. Its small size – less than 17000 Km2 – allows for rapid internal communication thanks to its efficient motorway system. The two airports (in addition to the nearby Brussels international airport) put the region less than two hours from most European destinations, most of which are generally accessible via low fare flights. The high speed train line which crosses the region also places its major cities (Charleroi, Namur and Liège) within a 2 hour proximity to Paris, London, Amsterdam and Frankfurt. AMSTERDAM THE HAGUE ROTTERDAM LONDON ANTWERP MAASTRICHT BRUSSELS MONS COLOGNE BONN LIEGE LILLE CHARLEROI NAMUR highways waterways FRANKFURT high speed train lines / TGV airports ports LUXEMBOURG PARIS Contact us BioWin a.s.b.l. | Point Centre | Avenue Georges Lemaître 19 | B-6041 Gosselies | Belgium T +32 (0)71 376 386 | F + 32 (0)71 376 387 | [email protected] visit www.biowin.org Resp. ed. | Frédéric Druck | Director Communication & International Relations | BioWin a.s.b.l. | Point Centre | Avenue Georges Lemaître 19 | B-6041 Gosselies | Belgium WALLONIA
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