Director: Dr. Georges Uzan
The Unit develops projects in the fields of hematology, wound healing, vascular system kidney biology by investigating the mutual interactions between respective stem cells and their microenvironments (niches). The research programs include basic science approaches as well as translational medicine applications. Clinical studies are focused on cell therapy for tissue repair and immuno-regulation of transplants. The mutual interactions between neoplastic stem cells (leukemia and kidney tumors) and their niches (bone marrow and kidney tissues) are also addressed.
The project of team 1 deals with the study of human mesenchymal, endothelial and hematopoietic stem cells and their organization within hematopietic stem cell (HSC) niches in fetus and adults. We work on the definition of their stem cell signature by analyzing their transcriptomic, proteomic and glycosylation profiles. We also study the role of mutual instructions in the maintenance of their stem cell properties, including quiescence, chemoresistance, proliferation and differentiation. Stem cell-niche interactions are analyzed in normal and pathological conditions, including aging, inflammation, heterotopic ossification and neoplasia (primary myelofibrosis and acute myeloid leukemia).
The team also addresses the topic of tissue repair of wounded or degenerated tissues. This includes cooperation of endothelial progenitors cells (EPC) and mesenchymal stromalcells (MSC) in the repair process in skin burns, bone defects and ischemia. There is a strong commitment to developing translational research.
The team investigates kidney diseases and their treatments through organ transplantation and kidney repair during various injuries or lesions. Following acute kidney injury, kidney may undergo either ad integrum restoration of function and structure but may also develop fibrosis. Kidney repair occurs through the expansion of stem cells or the de-differentiation of epithelial cells resistant to injury.
The project is divided in two parts: 1) the role of selected mediators like IL15, TGFb or cannabinoid receptors on progenitor activation and differentiation during tissue repair (normal kidney) or during renal tumor progression and their relation with kidney stem cell niche and microenvironment. 2) the study of mechanisms of allogeneic lymphocytes survival especially memory B cells and long lived plasma cells which are involved in chronic rejection in renal allogeneic transplantation partly mediated by donor specific antibodies and the effect of mesenchymal stem cells and the development of chronic rejection.
They will associate the skills of both teams to investigate novel strategies of tissue repair by cell therapy targeting ischemic diseases, large bone wound diseases, kidney rejection and severe thermal burns. The combined use of MSC, EPC and organ specific stem cells should allow improvement of already promising experimental and clinical trials.
These projects rely on 1) the academic research facilities provided by the Inserm structures and common platforms on the Paul-Brousse campus; 2) facilities for the production of clinical grade cell therapy products provided by the SSA structures; 3) Clinical departments: Department of Kidney transplantation at the CHU Bicêtre, Departments of hematology, severe burns and Orthopedy, Military Hospital of Percy).