Direct comparison of human mesenchymal stem cells derived from adipose tissues and bone marrow in mediating neovascularization in response to vascular ischemia.
OBJECTIVE
Although transplantation of MSC derived from bone marrow or adipose tissues has been shown in proangiogenic action in hindlimb ischemia model of nude mice, little information is available regarding comparison of the angiogenic potency between human adipose stromal cells (hADSC) and bone marrow stromal cells (hBMSC). We compared their therapeutic potential by transplantation of equal numbers of hADSC or hBMSC in a nude mice model of hindlimb ischemia.


RESULTS
One day after creating hindlimb ischemia, mice were randomized to receive hADSC transplantation (hADSC group), hBMSC transplantation (hBMSC group), or vehicle transplantation (Control group). Two weeks after transplantation, the laser Doppler perfusion index was significantly higher in the hADSC group and hBMSC group than in the control group. Comparison between hADSC and hBMSC group showed better recovery of blood flow in hADSC group than in hBMSC group. Conditioned media from hADSC (hADSC-CM) showed better in vitro tube formation of hADSC than conditioned media from hBMSC (hBMSC-CM). hADSC showed higher expression of MMP3 and MMP9 than hBMSC. A MMP inhibitor, GM6001, and the transfection of MMP3 or MMP9 siRNA oligonucleotides inhibited in vitro tube formation of hADSC. Transplantation of MMP3 or MMP9 siRNA oligonucleotieds-transfected hADSC showed lower blood flow recovery and higher tissue injury than control oligonucelotide-transfected cells.


CONCLUSIONS
This study showed that hADSC can be an ideal source for therapeutic angiogenesis in ischemic disease in terms of efficacy, accessibility and available tissue amounts.
Kim
Yeon
Y
Department of Physiology, School of Medicine, Pusan National University, Pusan, Korea.
Kim
Hoe
H
Cho
Hyun
H
Bae
Yong
Y
Suh
Kuen
K
Jung
Jin
J
D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology; D004338:Drug Combinations; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D007797:Laminin / Q000187:drug effects; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011509:Proteoglycans / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism
D004151:Dipeptides; D004338:Drug Combinations; D007797:Laminin; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011509:Proteoglycans; D034741:RNA, Small Interfering; C059485:matrigel; D003094:Collagen; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9