Mesenchymal Stem Cells Pretreated with Delivered Hph‐1‐Hsp70 Protein Are Protected from Hypoxia‐Mediated Cell Death and Rescue Heart Functions from Myocardial Injury
Mesenchymal stem cell (MSC) therapy for myocardial injury has inherent limitations due to the poor viability of MSCs after cell transplantation. In this study, we directly delivered Hsp70, a protein with protective functions against stress, into MSCs, using the Hph‐1 protein transduction domain ex v...
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Published in | Stem cells (Dayton, Ohio) Vol. 27; no. 9; pp. 2283 - 2292 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.09.2009
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Subjects | |
Online Access | Get full text |
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Summary: | Mesenchymal stem cell (MSC) therapy for myocardial injury has inherent limitations due to the poor viability of MSCs after cell transplantation. In this study, we directly delivered Hsp70, a protein with protective functions against stress, into MSCs, using the Hph‐1 protein transduction domain ex vivo for high transfection efficiency and low cytotoxicity. Compared to control MSCs in in vitro hypoxic conditions, MSCs delivered with Hph‐1‐Hsp70 (Hph‐1‐Hsp70‐MSCs) displayed higher viability and anti‐apoptotic properties, including Bcl2 increase, reduction of Bax, JNK phosphorylation and caspase‐3 activity. Hsp70 delivery also attenuated cellular ATP‐depleting stress. Eight animals per group were used for in vivo experiments after occlusion of the left coronary artery. Transplantation of Hph‐1‐Hsp70‐MSCs led to a decrease in the fibrotic heart area, and significantly reduced the apoptotic positive index by 19.5 ± 2%, compared to no‐treatment controls. Hph‐1‐Hsp70‐MSCs were well‐integrated into the infarcted host myocardium. The mean microvessel count per field in the infarcted myocardium of the Hph‐1‐Hsp70‐MSC‐treated group (122.1 ± 13.5) increased relative to the MSC‐treated group (75.9 ± 10.4). By echocardiography, transplantation of Hph‐1‐Hsp70‐MSCs resulted in additional increases in heart function, compared to the MSCs‐transplanted group. Our results may help formulate better clinical strategies for in vivo MSC cell therapy for myocardial damage. STEM CELLS 2009;27:2283–2292 |
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Bibliography: | First published online in STEM CELLS Telephone: 82‐2‐2123‐2889; Fax: 82‐2‐362‐7265 Disclosure of potential conflicts of interest is found at the end of this article. These authors contributed equally to this manuscript. June 18, 2009. Author contributions: W.C., B.‐W.S., S.L., H.S., C.Y.S., and J.H.C.: data collection and/or assembly of data, data analysis and interpretation; M.‐J.C., D.H.A., Y.‐G.J., D.‐H.L., K.‐D.C., and S.‐K.L.: provision of study material, data interpretation; N.C., S.‐K. L., and Y.J.: data interpretation, final approval of manuscript; K.‐C.H.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript. W.C. and B.‐W.S. contributed equally to this work. EXPRESS Telephone: 82‐2‐2228‐8445; Fax: 82‐2‐365‐1878 Telephone: 82‐2‐2228‐8523; Fax: 82‐2‐365‐1878 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1066-5099 1549-4918 |
DOI: | 10.1002/stem.153 |