Email: luc.douay@sat.aphp.fr

Proliferation and differentiation of stem cells

The team “Proliferation and differentiation of stem cells” has a long lasting international expertise in the field of hematopoietic Stem Cells (HSC) transplantation since 1978. Luc Douay is the Principal Investigator of the team “Proliferation and differentiation of stem cells: application to cell therapy” since 2007. The group has become a world pioneer and leader in the concept of cultured Red Blood Cells (cRBC) generated in vitro from stem cells for transfusion purpose and has first described all the major steps. Indeed, it has reported their large-scale production by designing a protocol, which permits the generation of fully functional mature RBC from HSC (Nat Biotechnol, 2002, 2005). It then developed GMP conditions for clinical grade production of cRBC for clinical study (3 patents). It recently achieved a world premiere: the first injection into human of cRBC for studying their lifespan. It demonstrated that cRBCs behaved similarly to transfused native RBCs, therefore establishing the proof of principle for transfusion medicine (Blood, 2011).

The team has made first demonstration of the interest of iPS as an unlimited source of cRBCs: the assessment of their capacity to complete differentiation in vitro into functional enucleated RBC (Haematologica, 2011); and the assessment of their capacity to achieve the complete switch of globin genes in vivo (Haematologica, 2012). In addition, the team has shown that only 3 IPS cell lines, cleverly chosen for their erythroid phenotype, would answer to more than 99% of transfusion situations (TMR, 2011) exhibiting the concept of universal blood source, (Current Op Hematology, 2011). Finally, the team has reported how this ex vivo model could be a tool for the fundamental study of erythropoiesis in a physiological (Plos One, 2012) and pathological context in myelodysplastic syndromes (Haematologica, 2010). Overall, our research activity has reached our main objective by successful transfer of this concept from Bench to Bed.

The research has been supported by several major national and international grants (EFS, US Army Defense Advanced Research Projects Agency (DARPA); DIM StemPole Ile de France; Foundation for medical research (FRM labelled team 2010); French National Agency for Research (ANR); FUI (Fonds unique interministériel, Pôle de compétitivité), OSEO attesting for our determination to achieve our final goal: the industrial production of RBCs for clinical application. They reflect the interest, the backing and the confidence of the national state institutions and industrial partners.

A key element of our research team is the strong partnership with the clinical haematology departments of the University Hospital. Our group also collaborates with the Institute of Radioprotection and Nuclear Safety (IRSN) for the research protocols and animal models, Assistance Publique-Hôpitaux de Paris (Public Hospitals of Paris), the European Center for Biostatistical and Epidemiological Evaluation in Haematopoietic Cell Therapy (CEREST-TC), the French Blood Center (EFS IdF).