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- Title
Mesenchymal Stem Cells Pretreated with Delivered Hph-l-Hsp70 Protein Are Protected from Hypoxia-Mediated Cell Death and Rescue Heart Functions from Myocardial Injury.
- Authors
Woochul Chang; Byeong-Wook Song; Soyeon Lim; Heesang Song; Chi Young Shim; Min-Ji Cha; Dong Hyuck Ahn; Young-Gook Jung; Dong-Ho Lee; Ji Hyung Chung; Ki-Doo Choi; Seung-Kyou Lee; Namsik Chung; Sang-Kyou Lee; Yangsoo Jang; Ki-Chul Hwang
- Abstract
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-l-Hsp70 (Hph-l-Hsp70-MSCs) displayed higher viability and anti-apoptotic properties, including Bcl2 increase, reduction of Bax, JNK phosphorylation and cas- pase-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-l-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-l-Hsp70-MSCs were well-integrated into the infarcted host myocardium. The mean microvessel count per field in the infarcted myocardium of the Hph-l-Hsp70-MSC- treated group (122.1 ▒ 13.5) increased relative to the MSC- treated group (75.9 ▒ 10.4). By echocardiography, transplantation of Hph-l-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
- Publication
Stem Cells, 2009, Vol 27, Issue 9, p2283
- ISSN
1066-5099
- Publication type
Academic Journal
- DOI
10.1002/stem.153