CTI-BIOTECH Bâtiment B1 5 Avenue Lionel TERRAY MEYZIEU-LYON FRANCE

Transcription

1 CTI-BIOTECH Bâtiment B1 5 Avenue Lionel TERRAY MEYZIEU-LYON FRANCE office@ctibiotech.com Tel : CONTACT : Professor Colin McGUCKIN, President, c.mcguckin@ctibiotech.com Dr Nico FORRAZ, Vice President, nico.forraz@ctibiotech.com Cell therapy and regenerative medicine are an emerging biomedical revolution. Procedures must be developed to enable repair of organs and tissues damaged by disease, life accidents or even treatments (chemotherapy, radiotherapy). CTI-BIOTECH, Cell Therapy research Institute contributes to the development of new cell therapies to advance the treatment of diseases such as cerebral palsy, stroke, diabetes, cancer, orthopaedic and craniofacial malformations, blood, immune system, liver and cardiovascular diseases. CTI-BIOTECH, Cell Therapy research Institute specializes in research on adult stem cells (bone marrow, fat) and from umbilical cord cells that have tremendous potential for tissue repair. CTI-BIOTECH, Cell Therapy research Institute implements a multidisciplinary approach to stimulate innovation with complementary research skills in cell biology, genetics, chemistry, biomaterials, engineering, nano-technologies, bio-imaging, multi-parametric flow cytometry, biophysics and bioethics. CTI-BIOTECH, Cell Therapy research Institute collaborates internationally with academic and industrial organizations to design clinical trials in regenerative medicine, cgmp procedures for cell therapy and bio-banking, development and validation of medical devices for cell therapy, production of cells and tissues for biomedical research, development of bio-assays and predictive models for molecular screening (pharmaceutical, biotechnology and cosmetics). Located at the crossroad of Europe in Lyon, CTI-BIOTECH missions include fundamental and applied biomedical research, innovation in biotechnology as well as education / training of responsible innovative researchers in collaboration with universities worldwide.

2 CTI-BIOTECH expertise grew from haematology and oncology research and patient based therapy including bone marrow disorders where stem cells fail to grow. Using Cord Blood and Bone Marrow, we use normal and abnormal stem cell populations to understand control mechanisms including cytokine and transcriptional pathways. This led us to investigate human adult and cord blood stem cells for haematology-oncology transplantation. The non-invasive nature of collection umbilical cord and cord blood offer a distinct advantage over any other sources of adult and embryonic stem cells. Umbilical cord and cord blood cells can be characterized and cryopreserved bio-banks worldwide. With over 130million children born each year, neonatal is an abundant stem cell source from all genetic and ethnic background. Our research has shown that cells from all three germ layers can be produced from umbilical cord, cord blood, fat and bone marrow stem cells. We have developed routine protocols for isolation of defined cell populations from extremely immature stem cell compartments, through to more mature progenitor cells, which have allowed defined tissue engineering and regenerative procedures to be advanced. The most significant development of our work has been the development of a protocol for the production of karyotypically normal Cord Bloodderived Embryonic-like stem cells (CBE s), which have the ability to form embryoid body-like structures and to express the majority of Embryonic Stem Cell markers. It is also possible to subculture these cells for ex vivo expansion for over 12 weeks, whilst maintaining their immaturity. This research,

3 published in 2005, is the first production of a clone of embryonic-like cells from a nonembryonic tissue. We further demonstrated the pluripotent nature of umbilical cord and cord blood stem cells that can be differentiated into endodermal, mesodermal and ectodermal tissues including neural, endothelial, hepatic, and pancreatic tissues. Conventional cell culture methods employ 2-dimensional culture systems to propagate cells in vitro. Although this approach is useful to understand key biological features like the cell cycle, growth factor stimulation, proliferation rates and signal transduction, the large scale clinical grade ex-vivo tissue and organ expansion generation calls for 3-dimensional Tissue Bio-engineering. Our preliminary work with bioreactors has demonstrated that they allow continuous rotation, expansion and endogenous extracellular matrix production in a shear stress-free environment favouring development into functional 3-D tissues. A key finding in this was our ability to expand, maintain and differentiate CBE s into hepatic and neural progenitors in 3-dimensions with and without supporting bio-scaffolds. CTI-BIOTECH host a team of 15 international researchers with extensive expertise in stem cell biology and cord blood bio-processing as well as stem cell cultures and tissue engineering. CTI-BIOTECH technical expertise includes 3-dimensional tissue engineering and bioreactor systems, flow cytometry, molecular biology, microarray, proteomics, laserscanning confocal microscopy, bio-processing. using adult (bone marrow, adipose tissues, cornea) and neonatal stem cells (umbilical cord, cord blood, placenta) as universal vectors for tissue engineering, drug screening, cell therapy and regenerative medicine research. PUBLICATIONS LIST CTI-BIOTECH. 1. Forraz N, Wright KE, Jurga M, and McGuckin CP (2011) Experimental therapies for repair of the central nervous system: stem cells and tissue engineering Nov in press. 2. Bhandari DR, Seo KW, Sun B, Seo MS, Kim HS, Seo YJ, Jurga M, Forraz N, Le Roy H, Denner L, McGuckin CP, Kang KS. (2011) The simplest method for in vitro β-cell production from human adult stem cells. Differentiation Oct;82(3): Epub 2011 Jul Jurga M, Forraz N, Basford C, Atzeni G, Trevelian AJ, Habibollah S, Ali H, Zwolinski SA, McGuckin C. (2011 Neurogenic properties and a clinical relevance of multipotent stem cells derived from cord blood samples stored in the biobanks. Stem Cells Dev Jul 6. [Epub ahead of print] 4. Ali H, Forraz N, McGuckin CP, Jurga M, Lindsay S, Ip BK, Trevelyan A, Basford C, Habibollah S, Ahmad S, Clowry GJ, Bayatti N. (2011) In Vitro Modelling of Cortical Neurogenesis by Sequential Induction of Human Umbilical Cord Blood Stem Cells. Stem Cell Rev Jun 16. [Epub ahead of print]

4 5. Perruisseau-Carrier C, Jurga M, Forraz N, McGuckin CP. (2011) mirnas Stem Cell Reprogramming for Neuronal Induction and Differentiation. Mol Neurobiol. 43(3): Forraz N, McGuckin CP. (2011) The umbilical cord: a rich and ethical stem cell source to advance regenerative medicine. Cell Prolif. 44 Suppl 1: Leeb C, Jurga M, McGuckin C, Forraz N, Thallinger C, Moriggl R, Kenner L. (2011) New perspectives in stem cell research: beyond embryonic stem cells. Cell Prolif. 44 Suppl 1: Jurga M, Dainiak MB, Sarnowska A, Jablonska A, Tripathi A, Plieva FM, Savina IN, Strojek L, Jungvid H, Kumar A, Lukomska B, Domanska-Janik K, Forraz N, McGuckin CP. (2011) The performance of laminin-containing cryogel scaffolds in neural tissue regeneration. Biomaterials. 32(13): Epub 2011 Feb Basford C, Forraz N, McGuckin C. (2010) Optimized multiparametric immunophenotyping of umbilical cord blood cells by flow cytometry. Nat Protoc Jul;5(7): Jurga M, Forraz N, McGuckin CP. (2010) Artificial human tissues from cord and cord blood stem cells for multi-organ regenerative medicine: viable alternatives to animal in vitro toxicology. Altern Lab Anim May;38(2): Basford, C., Forraz, N. Habibollah, S., Hanger, K., McGuckin, C.P., (2009) Umbilical cord blood processing with Prepacyte-CB increases haematopoietic progenitor cell availability over conventional Hetastarch separation. Cell Prolif. 42(6): Ali H, Jurga M, Kurgonaite K, Forraz N, McGuckin C. (2009) Defined serum-free culturing conditions for neural tissue engineering of human cord blood stem cells. Acta Neurobiol Exp 69(1): Aulisa, L., Forraz, N., McGuckin, C., Hartgerink, J;D. (2009) Inhibition of cancer cell proliferation by designed peptide amphiphiles. Acta Biomater. 5(3):

5 14. McGuckin, C.P., Jurga, M., Ali, H., Strbad, M., Forraz, N. (2008) Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro. Nature Protocols 3: McGuckin C.P., Forraz N. Umbilical cord blood stem cells-an ethical source for regenerative medicine. Med Law (2008) 27: McGuckin CP, Forraz N. Potential for access to embryonic-like cells from human umbilical cord blood.(2008) Cell Prolif. 41 Suppl 1: Jun, H.W., Paramonov, S.E., Dong, H., Forraz, N., McGuckin, C., Hartgerink, J.D. (2008) Tuning the mechanical and bioresponsive properties of peptideamphiphile nanofiber networks. J Biomater Sci Polym Ed. 19(5): McGuckin, C.P., Basford, C., Hanger, K., Habibollah, S., Forraz, N. (2007) Cord blood revelations: the importance of being a first born girl, big, on time and to a young mother! Early Hum Dev.;83(12): Denner, L., Bodenburg, Y., Zhao, J., Howe, M., Cappo, J., Tilton, R., Copland, J., Forraz, N., McGuckin, C., Urban, R. (2007) Directed engineering of adult umbilical cord blood stem cells to produce C-Peptide and Insulin. Cell Prolif. 40(3): Forde, S., Tye, B.J., Newey, S.E., Roubelakis, M., Smythe, J., McGuckin, C.P., Pettengell, R., Watt, S.M. (2007) Endolyn (CD164) modulates the CXCL12-mediated migration of umbilical cord blood CD133+ cells. Blood, 109, McGuckin, C.P., Forraz, N., Baradez, M.O., Basford, C., Dickinson, A.M., Navran, S., Hartgerink, J.D. (2006) Embryonic-like stem cells from umbilical cord blood and potential for neural modeling. Acta Neurobiologiae Experimentalis, 66, McGuckin, C.P., Forraz, N., Baradez, M.O., Navran, S., Zhao, J., Urban, R., Tilton, R. & Denner, L. (2006) Embryonic stem cells from human umbilical cord blood. Tissue Engineering, 12, Forraz, N., Baradez, M.O. & McGuckin, C.P. (2006) Characterization of the first umbilical cord blood multi lineage progenitor cell (TM) line by high definition microarray. Tissue Engineering, 12, McGuckin, C.P., Forraz, N., Baradez, M.O., Navran, S., Zhao, J., Urban, R., Tilton, R. & Denner, L. (2005) Production of stem cells with embryonic characteristics from human umbilical cord blood. Cell Proliferation, 38, Russomano T., Cardoso RB, Falcão FP, Dalmarco G, dos Santos C.RV, dos Santos L.G.F., de Azevedo D.F.G., dos Santos M.A., Martinelli M.A., Motta J.D., Forraz N., McGuckin C.P.

6 (2005) Development and Validation of a 3D Clinostat for the Study of Cells during Microgravity Simulation. IEEE inmedicine and Biology 1, Forraz, N., Pettengell, R. & McGuckin, C.P. (2004) Characterization of a lineagenegative stem-progenitor cell population optimized for ex vivo expansion and enriched for LTC-IC. Stem Cell, 22, McGuckin, C.P., Forraz, N., Allouard, Q. & Pettengell, R. (2004) Umbilical cord blood stem cells can expand hematopoietic and neuroglial progenitors in vitro. Experimental Cell Research, 295, McGuckin, C. P.; Forraz, N.; Pettengell, R.; Thompson, A. (2004) Thrombopoietin, flt3-ligand and c-kit-ligand modulate HOX gene expression in expanding cord blood CD133 cells. Cell Proliferation, 37, McGuckin, C.P., Pearce, D., Forraz, N., Tooze, J.A., Watt, S.M. & Pettengell, R. (2003) Multiparametric analysis of immature cell populations in umbilical cord blood and bone marrow. European Journal of Haematology, 71, Whiting, K. A.; McGuckin, C. P.; Wertheim, D.; Pearce, D.; Pettengell, R. (2003) Three-dimensional analysis of CD34 sialomucin distribution on cord blood and bone marrow. British Journal of Haematology 2003, 122, McGuckin, C. P.; Forraz, N.; Liu, W. M. (2003) Diaminofluorene stain detects erythroid differentiation in immature haemopoietic cells treated with EPO, IL-3, SCF, TGFbeta1, MIP-1alpha and IFNgamma. European Journal of Haematology 70, McGuckin, C. P.; Forraz, N.; Baradez, M. O.; Lojo-Rial, C.; Wertheim, D.; Whiting, K.; Watt, S. M.; Pettengell, R. (2003) Colocalization analysis of sialomucins CD34 and CD164. Stem Cells, 21, McGuckin, C. P.; Pearce, D.; Forraz, N.; Tooze, J. A.; Watt, S. M.; Pettengell, R. (2003) Multiparametric analysis of immature cell populations in umbilical cord blood and bone marrow. European Journal of Haematology, 71, Forraz, N.; Pettengell, R.; Deglesne, P. A.; McGuckin, C. P. (2002) AC133+ umbilical cord blood progenitors demonstrate rapid self-renewal and low apoptosis. British Journal of Haematology, 119, Forraz, N.; Pettengell, R.; McGuckin, C. P. (2002) Haemopoietic and neuroglial progenitors are promoted during cord blood ex vivo expansion. British Journal of Haematology, 119, J.C.W.Marsh and C.P.McGuckin. Cytokine stimulation of Diamond Blackfan Anaemia Bone Marrow. International Journal of Pediatric Hematology/Oncology, pp. 1-7, C.P.McGuckin, W-M.Liu, E.C.Gordon-Smith and M.R.Uhr. A novel approach to investigating the erythroid lineage, using both receptor analysis and haemoglobin detection. British Journal of Haematology 95, pp , 1996.

7 38. A.R.Miresluis, R.G.Das, R.Thorpe, S.Thomas, D.Maher, P.Valent, D.Groote, K.Hayglass, H.Ziltener, L.K.Poulsen, P.Miossec, P.Chromarat, J.Grassi, G.Pawelec, U.Fritzsche, M.Falk, M.Topp, G.Reisbach, J.Sidiropoulos, S.Z.Benasson, Z.Evenchen, L.Pegoraro, F.Barboni, K.Sugimoto, K.Tsuji, T.Matsumoto, K.Arai, T.Yokota, J.Olobo, G.Wagemaker, T.Vanderpouwkraan, K.V.Sheth, C.Gutierrez, D.Rivas, N.Lycke, K.Schon, J.P.A.Bews, K.Tullberg, R.Klotzbucher, L.Page, C.Bird, C.P.McGuckin, J.Gordon, A.Katira, P.Openshaw, A.Georgiou, N.G.Testa, R.Callard, K.Paik, J.McKearn, M.Rock, K.Harper, S.J.Swanson, J.P.Siegel, H.L.Speigelberg, J.Geigert, K.Carter, W.E.Paul, C.Watson, M.Tsang, L.Zhou, L.Weistreich, C.C.Chao, T.L.Riss, R.Moravec Implications for the assay and biological activity of Interleukin-4 - Results of a WHO international collaborative study. Journal of Immunological Methods 194, (1), pp.13-25, A.R.Miresluis, R.G.Das, R.Thorpe, S.Thomas, D.Maher, P.Valent, E.Payer, D.Groote, K.Hayglass, H.Ziltener, L.K.Poulsen, P.Miossec, P.Chromarat, J.Grassi, G.Pawelec, U.Fritzsche, M.Falk, M.Topp, G.Reisbach, J.Sidiropoulos, S.Z.Benasson, Z.Evenchen, L.Pegoraro, F.Barboni, K.Sugimoto, K.Tsuji, K.Arai, T.Yokota, J.Olobo, G.Wagemaker, T.Vanderpouwkraan, K.V.Sheth, C.Gutierrez, D.Rivas, N.Lycke, K.Schon, J.P.A.Bews, K.Tullberg, R.Klotzbucher, L.Page, C.Bird, C.P.McGuckin, J.Gordon, A.Katira, P.Openshaw, A.Georgiou, N.G.Testa, R.Callard, K.Paik, J.McKearn, M.Rock, K.Harper, S.J.Swanson, J.P.Siegel, H.L.Speigelberg, J.Geigert, K.Carter, W.E.Paul, C.Watson,M.Tsang, L.Zhou, L.Weistreich, C.C.Chao, T.L.Riss, R.Moravec.Implications for the assay and biological properties of Interleukin-3 - Results of a WHO international collaborative study. Journal of Immunological Methods 194, (1), pp.1-12, S.E.Ball, C.P.McGuckin, G.Jenkins and E.C.Gordon-Smith. Diamond Blackfan anaemia in the UK: analysis of 80 cases from a 20-year cohort. British Journal of Haematology 94, pp , C.P.McGuckin, M.R.Uhr, W-M.Liu and E.C.Gordon-Smith.The use of recombinant SCF protein for rapid determination of c-kit expression in normal and abnormal erythropoiesis. European Journal of Haematology 57, pp.72-78, C.P.McGuckin, M.R. Uhr, S.E.Ball, E.C.Gordon-Smith. In vitro progenitor analysis in a Diamond Blackfan Anaemia patient who responded once but not twice to Interleukin-3 therapy, using short-term and long-term cultures and c-kit analysis. British Journal of Haematology 93, pp , C.P.McGuckin, Wai M.Liu, S.E. Ball, E.C.Gordon-Smith and M.R.Uhr. Diamond Blackfan Anaemia: Differential pattern of in vitro progenitor response to Macrophage Inflammatory Protein 1- alpha. British Journal of Haematology 92, pp , 1996

8 44. C.P.McGuckin, S.E.Ball and E.C.Gordon-Smith. Diamond Blackfan Anaemia: In vitro erythroid history of a previous IL-3 responder who failed to respond to a second IL-3 treatment following relapse. Experimental Hematology Today (requested conference volume). 45. J.Scopes, S.Daly, S.E.Ball, C.P.McGuckin, E.C.Gordon-Smith and F.M.Gibson. The effect of human FLT-3 ligand on committed progenitor cell production from Aplastic Anaemia and Diamond Blackfan Anaemia bone marrow. British Journal of Haematology 91, pp , P.D.W.Kiely, C.P.McGuckin, D.A.Collins, D.H.Bevan and J.C.W.Marsh. Erythrocyte Aplasia and Systemic Lupus Erythematosus. Lupus 4, (5) pp , C.P.McGuckin, S.E.Ball, E.C.Gordon-Smith.Diamond Blackfan Anaemia: three patterns of in vitro response to haemopoietic growth factors. British Journal of Haematology 89, pp , C.P.McGuckin, M.R.Uhr and E.C.Gordon-Smith. c-kit protein (Stem Cell Factor receptor) expression on cells with erythroid characteristics and on normal human bone marrow, without the use of monoclonal antibodies. Experimental Hematology (USA) 23, pp , H.D.Schaufelberger, M.R.Uhr, C.P.McGuckin, R.P.H.Logan, J.J.Misiewicz, E.C.Gordon-Smith & C.Beglinger. Platelets in ulcerative colitis and Crohn's disease express functional interleukin-1 and interleukin-8 receptors. European Journal of Clinical Investigation. 24, pp , Y.Bastion, P.Bordigoni, M.Debre, D.Girault, T.Leblanc, G.Tchernia, S.Ball, C.McGuckin, E.C.Gordon-Smith, A.Bekassy, G.Elinder, L.Wranne and M.Lanning. Sustained response after recombinant interleukin-3 in Diamond Blackfan Anemia. Blood 83 (2) pp C.P.McGuckin, N.D.Cunningham,, M.McCabe, C.Adams, and W.S.Gilmore. Some properties of the plasma membrane receptor for granulocyte colony stimulating factor (G-CSF). Biochemical Society Transactions 18 p.290, 1990.

9 52. W.S.Gilmore, B.M.Hannigan, S.J.Eason, C.P.McGuckin and A.A.Nelson. Recombinant human granulocyte colony-stimulating factor (rhgcsf) and superoxide production in a haemopoietic cell line. Biochemical Society Transactions 19 p.237, W.S.Gilmore and C.P.McGuckin. High performance liquid chromatography of human urinary colony-stimulating factors Biochemical Society Transactions 17 pp.602-3, 1989.