title: Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement.
abstract: 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.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, PR China. zengbin19982005@yahoo.com.cn
authors.forename: Bin
authors.initials: B
authors.lastname: Zeng
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Ren
authors.forename: Guosheng
authors.initials: G
authors.lastname: Lin
authors.forename: Chengang
authors.initials: C
authors.lastname: Zhu
authors.forename: Honglei
authors.initials: H
authors.lastname: Chen
authors.forename: Jiechao
authors.initials: J
authors.lastname: Yin
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Danhua
authors.initials: D
authors.lastname: Ding
mesh_terms: 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
chemical_list: D002316:Cardiotonic Agents; D016207:Cytokines; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1