MAPC transplantation confers a more durable benefit than AC133+ cell transplantation in severe hind limb ischemia
Aranguren XL, Pelacho B, Peñuelas I, Abizanda G, Uriz M, Ecay M, Collantaes M, Araña M, Beerens M, Coppiello G, Prieto I, Perez-Ilzarbe M, Andreu EJ, Luttun A, Prósper F.
Hematology Service and Cell Therapy, Foundation for Applied Medical Research, Division of Cancer, University of Navarra, Pamplona, Spain
There is a need for comparative studies to determine which cell types are better candidates to remedy ischemia. Here, we compared human AC133(+) cells and multipotent adult progenitor cells (hMAPC) in a mouse model reminiscent of critical limb ischemia.
hMAPC or hAC133(+) cell transplantation induced a significant improvement in tissue perfusion (measured by microPET) 15 days posttransplantation compared to controls. This improvement persisted for 30 days in hMAPC-treated but not in hAC133(+)-injected animals.
While transplantation of hAC133(+) cells promoted capillary growth, hMAPC transplantation also induced collateral expansion, decreased muscle necrosis/fibrosis, and improved muscle regeneration. Incorporation of differentiated hAC133(+) or hMAPC progeny into new vessels was limited; however, a paracrine angio/arteriogenic effect was demonstrated in animals treated with hMAPC. Accordingly, hMAPC-conditioned, but not hAC133(+)-conditioned, media stimulated vascular cell proliferation and prevented myoblast, endothelial, and smooth muscle cell apoptosis in vitro.
Our study suggests that although hAC133(+) cell and hMAPC transplantation both contribute to vascular regeneration in ischemic limbs, hMAPC exert a more robust effect through trophic mechanisms, which translated into collateral and muscle fiber regeneration. This, in turn, conferred tissue protection and regeneration with longer term functional improvement.
CITATION Cell Transplant. 2011;20(2):259-69. Epub 2010 Aug 17