Mesenchymal stem cells rescue CD34+ cells from radiation-induced apoptosis and sustain hematopoietic reconstitution after coculture and cografting in lethally irradiated baboons: is autologous stem cell therapy in nuclear accident settings hype or reality?
Autologous stem cell therapy (ACT) has been proposed to prevent irradiated victims from bone marrow (BM) aplasia by grafting hematopoietic stem and progenitor cells (HSPCs) collected early after damage, provided that a functional graft of sufficient size could be produced ex vivo. To address this issue, we set up a baboon model of cell therapy in which autologous peripheral blood HSPCs collected before lethal total body irradiation were irradiated in vitro (2.5 Gy, D0 1 Gy) to mimic the cell damage, cultured in small numbers for a week in a serum-free medium in the presence of antiapoptotic cytokines and mesenchymal stem cells (MSCs) and then cografted. Our study shows that baboons cografted with expanded cells issued from 0.75 and 1 x 10(6)/kg irradiated CD34+ cells and MSCs (n=2) exhibited a stable long-term multilineage engraftment. Hematopoietic recovery became uncertain when reducing the CD34+ cell input (0.4 x 10(6)/kg CD34+ cells; n=3). However, platelet recovery was accelerated in all surviving cografted animals, when compared with baboons transplanted with unirradiated, unmanipulated CD34+ cells (0.5-1 x 10(6)/kg, n=4). Baboons grafted with MSCs alone (n=3) did not recover. In all cases, the nonhematopoietic toxicity remained huge. This baboon study suggests that ACT feasibility is limited.
Drouet
M
M
Centre de Recherches du Service de Santé des Armées, La Tronche, France. micheldrouet@crssa.net
Mourcin
F
F
Grenier
N
N
Delaunay
C
C
Mayol
J F
JF
Lataillade
J J
JJ
Peinnequin
A
A
Hérodin
F
F
D000818:Animals; D018952:Antigens, CD34; D017209:Apoptosis / Q000528:radiation effects; D002450:Cell Communication; D018929:Cell Culture Techniques; D018920:Coculture Techniques; D006085:Graft Survival; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000528:radiation effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D023421:Models, Animal; D010215:Papio; D011832:Radiation Injuries / Q000628:therapy*; D018788:Radioactive Hazard Release; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation
D018952:Antigens, CD34