Genistein promotes endothelial colony-forming cell (ECFC) bioactivities and cardiac regeneration in myocardial infarction.
Although stem cell-mediated treatment of ischemic diseases offers significant therapeutic promise, the limitation in the therapeutic efficacy of transplanted stem cells in vivo because of poor engraftment remains a challenge. Several strategies aimed at improving survival and engraftment of stem cells in the ischemic myocardium have been developed, such as cell transplantation in combination with growth factor delivery, genetic modification of stem cells, and/or cell therapy using scaffolds. To improve therapeutic efficacy, we investigated the effects of genistein on the engraftment of transplanted ECFCs in an acute myocardial ischemia model.


RESULTS
We found that genistein treatment enhanced ECFCs' migration and proliferation, which was accompanied by increases in the expression of ILK, α-parvin, F-actin, and phospholylation of ERK 1/2 signaling. Transplantation of genistein-stimulates ECFCs (GS-ECFCs) into myocardial ischemic sites in vivo induced cellular proliferation and secretion of angiogenic cytokines at the ischemic sites and thereby enhanced neovascularization and decreased myocardial fibrosis as well as improved cardiac function, as shown by echocardiography. Taken together, these data suggest that pretreatment of ECFCs with genistein prior to transplantation can improve the regenerative potential in ischemic tissues, providing a novel strategy in adult stem cell therapy for ischemic diseases.
Medical Science Research Institute Soonchunhyang University Seoul Hospital Seoul, Korea; Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University Yangsan, Korea; Department of Medical Bioscience, Soonchunhyang University Asan, Asan, Korea.
Sang Hun
SH
Lee
Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University Yangsan, Korea; Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Department of Physiology, School of Medicine, Pusan National University Yangsan, Korea.
Jun Hee
JH
Lee
Stem Cell Translational Research, Institute of Biomedical Research and Innovation/RIKEN Center for Developmental Biology, Kobe, Japan; Department of Regenerative Medicine Science, Tokai University School of Medicine, Isehara, Japan.
Takayuki
T
Asahara
Heart Research Center, Chonnam National University Hospital, Gwangju, Korea.
Yong Sook
YS
Kim
Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea.
Hae Chang
HC
Jeong
Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea.
Youngkeun
Y
Ahn
Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam, Korea.
Jin Sup
JS
Jung
Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University Yangsan, Korea; Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Department of Physiology, School of Medicine, Pusan National University Yangsan, Korea.
Sang-Mo
SM
Kwon
D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D004452:Echocardiography; D042783:Endothelial Cells / Q000166:cytology* / Q000637:transplantation; D005312:Fetal Blood; D019833:Genistein / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007511:Ischemia; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000378:metabolism; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D009389:Neovascularization, Pathologic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012038:Regeneration; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D000099200:Scaffold Protein ILK; D000096985:Calponins
D000199:Actins; D016207:Cytokines; D019833:Genistein; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C486590:PARVA protein, human; D000096985:Calponins; C519774:Parva protein, mouse