Expansion des cellules souches hématopoïétiques dans les systèmes de cocultures des cellules endothéliales et des cellules stromales

Abstract : Ex vivo expansion of hematopoietic stem cells may shorten neutrophil or platelet regeneration after myeloablative chemoradiotherapy, provide a prolonged time period for retroviral infection for gene transfer into hematopoietic progenitor, and improve the quality of an autograft in progenitor cell transplantation by selective stimulation of residual healthy progenitors with repopulation capacity.To optimize conditions for ex vivo expansion of peripheral progenitor cells, we explored the feasibility of periperal CD34+ cells expansion invitro in coculture systems using the different stromal (OP9, MSC) and endothelial (HUVEC) cells. We showed that the cocultures with OP9, HUVEC and MSC allowed an amplification of the peripheral CD34+ cells more durable and more significant than the cultures in cytokines. We appoinled that IL-6 secreted by MSC and BUVEC contribute partially for these positive purposes for the expansion of the CSS. In addition, the MSC also decrease the allostimulatory capacily of the HSC amplified, which supports the tolerance of the graft. In addition, the OP9 support the expansion of the CSS thanks to tlheir deficit of the production of monocytes/macrophages. These models of coculture seem interesting for better including/underslanding the regulating mechanisms of the hematopoiesis and also the inhibiting factors, for example in the physiopathology of the syndromes myelodysplasic. In conclusion, our work enables us to better include/understand the regulation of the hematopoiesis and provides us protocols usable in private clinic for the expansion of the in vitro HSC.
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Theses
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http://docnum.univ-lorraine.fr/prive/SCD_T_2005_0232_LI.pdf
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https://hal.univ-lorraine.fr/tel-01746995
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Submitted on : Thursday, March 29, 2018 - 10:49:11 AM
Last modification on : Friday, March 30, 2018 - 1:28:22 AM

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Na Li. Expansion des cellules souches hématopoïétiques dans les systèmes de cocultures des cellules endothéliales et des cellules stromales. Sciences agricoles. Université Henri Poincaré - Nancy 1, 2005. Français. ⟨NNT : 2005NAN11320⟩. ⟨tel-01746995⟩

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