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Présentation UMRS1197_en

UMR-S 1197 Inserm/University Paris Sud/Health Department of the Armies
Interactions between stem cells and their niches in physiology, tumors and tissue repair
 

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 team 1 project deals with the interactions of hematopoietic, endothelial and mesenchymal stem cells within their common niches in normal or pathological (neoplastic or not).
The team 2 project focuses on normal and pathological renal microenvironments and on immune graft-host interactions within the kidney.
The Unit is a joint laboratory between Inserm and the Health Department of the Armies (Service de Santé des Armées, SSA).
 
Team 1: Stem cell-niche mutual interactions
Team leader : Georges Uzan
 

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.

Project 1 : Hematopoietic stem cell niches: the paradigm of HSC, MSC and EPC mutual interactions
(Marie-Caroline Le Bousse-Kerdilès, DR Inserm, This email address is being protected from spambots. You need JavaScript enabled to view it. )
Project 2 : Endothelial cell properties and specialization in tissue niches
(Georges Uzan, DR CNRS, This email address is being protected from spambots. You need JavaScript enabled to view it.)
 Project 3 : Immuno-modulatory effect of MSCs and MSC-derived products in tissular niches(Jean-Jacques Lataillade, Pr, This email address is being protected from spambots. You need JavaScript enabled to view it.)
 
Team 2: Stem cells, Transplantation, Immunoregulation  
Team leader : Antoine Dürrbach
 

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.

Project 1 : Involvement of the microenvironment in renal cancer and kidney injury
1-1 The microenvironment of renal tumors: Julien Giron-Michel, CR Inserm, This email address is being protected from spambots. You need JavaScript enabled to view it.; Pierre Eid, DR Inserm. This email address is being protected from spambots. You need JavaScript enabled to view it.
1-2 Involvement of microenvironments during various models of kidney injury: Hélène François, PU-PH, This email address is being protected from spambots. You need JavaScript enabled to view it.; Antoine Durrbach, PU-PH, This email address is being protected from spambots. You need JavaScript enabled to view it.
Project 2 : Prevention of chronic allograft dysfunction
Antoine Durrbach, PU-PH
 

Translational projects

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).

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