Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement.
The aim has been to determine whether the supernatants of mesenchymal stem cells (MSCs) transfected with adenovirus carrying human heme oxygenase-1 (hHO-1) gene protect cardiomyocytes from ischemic injury. We have found that hHO-1 infected MSCs (hHO-1-MSCs) increased expression of hHO-1 protein. Apoptosis of cultured hHO-1-MSCs exposed to hypoxia was suppressed. Several cytokines, including HGF, bFGF, TGF-beta, VEGF and IL-1beta, were produced by hHO-1-MSCs, some being significantly enhanced under hypoxia stimulation. Meanwhile, those cytokines reduced caspase-3 level and activity in cultured adult rat ventricular cardiomyocytes (ARVCs) exposed to hypoxia. Supernatants obtained from hHO-1-MSCs improved left ventricular function, limited myocardial infarct size, increased microvessel density, and inhibited apoptosis of cardiomyocytes in rat myocardial infarction. It can be concluded hHO-1-modified MSCs prevent myocardial cell injury via secretion of paracrine-acting mediators.
Zeng
Bin
B
Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, PR China. zengbin19982005@yahoo.com.cn
Ren
Xiaofeng
X
Lin
Guosheng
G
Zhu
Chengang
C
Chen
Honglei
H
Yin
Jiechao
J
Jiang
Hong
H
Yang
Bo
B
Ding
Danhua
D
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002316:Cardiotonic Agents / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004452:Echocardiography; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D016207:Cytokines; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1