Skeletal myosphere-derived progenitor cell transplantation promotes neovascularization in delta-sarcoglycan knockdown cardiomyopathy.
Bone marrow cells have been shown to contribute to neovascularization in ischemic hearts, whereas their impaired maturation to restore the delta-sarcoglycan (delta-SG) expression responsible for focal myocardial degeneration limits their utility to treat the pathogenesis of cardiomyopathy. Here, we report the isolation of multipotent progenitor cells from adult skeletal muscle, based on their ability to generate floating-myospheres. Myosphere-derived progenitor cells (MDPCs) are distinguishable from myogenic C2C12 cells and differentiate into vascular smooth muscle cells and mesenchymal progeny. The mutation in the delta-SG has been shown to develop vascular spasm to affect sarcolemma structure causing cardiomyopathy. We originally generated delta-SD knockdown (KD) mice and transplanted MDPCs into the hearts. MDPCs enhanced neoangiogenesis and restored delta-SG expression in impaired vasculatures through trans-differentiation, leading to improvement of cardiac function associated with paracrine effectors secretion. We propose that MDPCs may be the promising progenitor cells in skeletal muscle to treat delta-sarcoglycan complex mutant cardiomyopathy.
Nomura
Tetsuya
T
Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan.
Ashihara
Eishi
E
Tateishi
Kento
K
Asada
Satoshi
S
Ueyama
Tomomi
T
Takahashi
Tomosaburo
T
Matsubara
Hiroaki
H
Oh
Hidemasa
H
D000818:Animals; D009202:Cardiomyopathies / Q000473:pathology* / Q000601:surgery*; D002454:Cell Differentiation; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032446:Myoblasts / Q000166:cytology* / Q000637:transplantation*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D049031:Sarcoglycans / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D016896:Treatment Outcome
D049031:Sarcoglycans