Muscle-derived stem cells promote angiogenesis and attenuate intimal hyperplasia in different murine vascular disease models.
Muscle-derived stem cells (MDSCs) are known to promote angiogenesis, but have never been studied in vascular diseases. We differentiated MDSCs into endothelial lineage cells in vitro by stimulation with shear stress and vascular endothelial growth factor. Such differentiated MDSCs (diff-MDSC) showed strong angiogenic potential in vitro. When tested in ischemic hindlimbs of mice, diff-MDSCs increased perfusion and decreased necrosis of the ischemic limbs, by promoting new vessel formation and by upregulating genes involved in endothelial expression. Such effects were not observed with native MDSCs (without endothelial stimulation in vitro). Diff-MDSCs were also injected into carotid arteries of rats after balloon denudation of the intima layer to induce intimal hyperplasia. The cell-treated group had significantly reduced intima-to-media thickness ratio compared to control, thus attenuating intimal hyperplasia by early re-endothelialization of the intima layer. Our findings suggest that MDSCs are a potential source of stem cell therapy for treatment of various vascular diseases, by inducing angiogenesis to improve perfusion in sites of ischemia, and by preventing intimal hyperplasia in sites of vessel injury.
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Bundang-gu, Gyeonggi-do, Korea.
Hyung Sub
HS
Park
Soli
S
Hahn
Geum Hee
GH
Choi
Young Sun
YS
Yoo
Ji Youl
JY
Lee
Taeseung
T
Lee
D053687:Adult Stem Cells / Q000637:transplantation*; D000818:Animals; D002339:Carotid Arteries / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D006614:Hindlimb / Q000098:blood supply*; D006965:Hyperplasia / Q000628:therapy; D007511:Ischemia / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000473:pathology*; D014945:Wound Healing