title: Mesenchymal stem cells support expansion of in vitro irradiated CD34(+) cells in the presence of SCF, FLT3 ligand, TPO and IL3: potential application to autologous cell therapy in accidentally irradiated victims.
abstract: Ex vivo expansion of residual autologous hematopoietic stem and progenitor cells collected from victims soon after accidental irradiation (autologous cell therapy) may represent an additional or alternative approach to cytokine therapy or allogeneic transplantation. Peripheral blood CD34+ cells could be a useful source of cells for this process provided that collection and ex vivo expansion of hematopoietic stem and progenitor cells could be optimized. Here we investigated whether mesenchymal stem cells could sustain culture of irradiated peripheral blood CD34+ cells. In vitro irradiated (4 Gy 60Co gamma rays) or nonirradiated mobilized peripheral blood CD34+ cells from baboons were cultured for 7 days in a serum-free medium supplemented with stem cell factor+thrombopoietin+interleukin 3+FLT3 ligand (50 ng/ml each) in the presence or absence of mesenchymal stem cells. In contrast to cultures without mesenchymal stem cells, irradiated CD34+ cells cultured with mesenchymal stem cells displayed cell amplification, i.e. CD34+ (4.9-fold), CD34++ (3.8-fold), CD34++/Thy-1+ (8.1-fold), CD41+ (12.4-fold) and MPO+ (50.6-fold), although at lower levels than in nonirradiated CD34+ cells. Fourteen times more clonogenic cells, especially BFU-E, were preserved when irradiated cells were cultured on mesenchymal stem cells. Moreover, we showed that the effect of mesenchymal stem cells is related mainly to the reduction of apoptosis and involves cell-cell contact rather than production of soluble factor(s). This experimental model suggests that mesenchymal stem cells could provide a crucial tool for autologous cell therapy applied to accidentally irradiated victims.
authors.affiliation: Centre de Recherches du Service de Santé des Armées, La Tronche, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mourcin
authors.forename: Nancy
authors.initials: N
authors.lastname: Grenier
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mayol
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lataillade
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Sotto
authors.forename: Francis
authors.initials: F
authors.lastname: Hérodin
authors.forename: Michel
authors.initials: M
authors.lastname: Drouet
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D016207:Cytokines / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010215:Papio; D011832:Radiation Injuries / Q000601:surgery; D011836:Radiation Tolerance / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods
chemical_list: D018952:Antigens, CD34; D016207:Cytokines