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Integrin-linked kinase is required in hypoxic mesenchymal stem cells for strengthening cell adhesion to ischemic myocardium

Authors
 SUK-WON SONG  ;  WOOCHUL CHANG  ;  BYEONG-WOOK SONG  ;  HEESANG SONG  ;  SOYEON LIM  ;  HYE-JUNG KIM  ;  MIN-JI CHA  ;  EUNJU CHOI  ;  SIN-HYEOG IM  ;  BYUNG-CHUL CHANG  ;  NAMSIK CHUNG  ;  YANGSOO JANG  ;  KI-CHUL HWANG 
Citation
 Stem Cells, Vol.27(6) : 1358-1365, 2009 
Journal Title
 Stem Cells 
ISSN
 1066-5099 
Issue Date
2009
Abstract
Mesenchymal stem cells (MSCs) therapy has limitations due to the poor viability of MSCs after cell transplantation. Integrin-mediated adhesion is a prerequisite for cell survival. As a novel anti-death strategy to improve cell survival in the infarcted heart, MSCs were genetically modified to overexpress integrin-linked kinase (ILK). The survival rate of ILK-transfected MSCs (ILK-MSCs) was augmented by about 1.5-fold and the phosphorylation of ERK1/2 and Akt in ILK-MSCs were increased by about three and twofold, respectively. ILK-MSCs demonstrated an increase of twofold in the ratio of Bcl-2/Bax and inhibited caspase-3 activation, compared with hypoxic MSCs. The adhesion rate of ILK-MSCs also had a 32.2% increase on the cardiac fibroblast-derived three-dimensional matrix and ILK-MSCs showed higher retention by about fourfold compared to unmodified MSCs. Six animals per group were used for the in vivo experiments analyzed at 1 week after occlusion of the left coronary artery. ILK-MSC transplanted rats had a 12.0% +/- 3.1% smaller infarct size than MSC-treated rats after ligation of left anterior descending coronary artery. Transplantation of ILK-MSCs not only led to a 16.0% +/- 0.4% decrease in the fibrotic heart area, but also significantly reduced the apoptotic positive index by two-thirds when compared with ligation only. The mean microvessel count per field in the infarcted myocardium of ILK-MSCs group was increased relative to the sham group and MSCs group. In conclusion, the ILK gene transduction of MSCs further assisted cell survival and adhesion, and improved myocardial damage when compared with MSC only after transplantation.
Files in This Item:
T200902469.pdf Download
DOI
10.1002/stem.47
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
송병욱(Song, Byeong Wook)
송석원(Song, Suk Won) ORCID logo https://orcid.org/0000-0002-9850-9707
장병철(Chang, Byung Chul)
장양수(Jang, Yang Soo) ORCID logo https://orcid.org/0000-0002-2169-3112
장우철(Chang, Woo Chul)
정남식(Chung, Nam Sik)
황기철(Hwang, Ki Chul)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104224
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