Mesenchymal stem cells pretreated with delivered Hph-1-Hsp70 protein are protected from hypoxia-mediated cell death and rescue heart functions from myocardial injury

Woochul Chang, Byeong Wook Song, Soyeon Lim, Heesang Song, Young Shim Chi, Min Ji Cha, Hyuck Ahn Dong, Young Gook Jung, Dong Ho Lee, Hyung Chung Ji, Ki Doo Choi, Seung Kyou Lee, Namsik Chung, Sang Kyou Lee, Yangsoo Jang, Ki Chul Hwang

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

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-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 theMSCs-transplanted group. Our results may help formulate better clinical strategies for in vivo MSC cell therapy for myocardial damage.

Original languageEnglish
Pages (from-to)2283-2292
Number of pages10
JournalStem Cells
Volume27
Issue number9
DOIs
Publication statusPublished - 2009 Sep

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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