MAPC transplantation confers a more durable benefit than AC133+ cell transplantation in severe hind limb ischemia.
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.
Aranguren
Xabier L
XL
Hematology Service and Cell Therapy, Foundation for Applied Medical Research, Division of Cancer, University of Navarra, Pamplona, Spain.
Pelacho
Beatriz
B
Peñuelas
Ivan
I
Abizanda
Gloria
G
Uriz
Maialen
M
Ecay
Margarita
M
Collantaes
María
M
Araña
Miriam
M
Beerens
Manu
M
Coppiello
Giulia
G
Prieto
Inés
I
Perez-Ilzarbe
Maitane
M
Andreu
Enrique J
EJ
Luttun
Aernout
A
Prósper
Felipe
F
D000071916:AC133 Antigen; D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis; D001808:Blood Vessels / Q000254:growth & development; D049109:Cell Proliferation; D019610:Cytoprotection; D006023:Glycoproteins / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D039902:Multipotent Stem Cells / Q000166:cytology*; D009132:Muscles / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000378:metabolism*; D012038:Regeneration; D015424:Reperfusion; D033581:Stem Cell Transplantation; D014022:Tissue Survival
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse