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

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

Research output: Contribution to journalArticle

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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 two-fold 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.

Original languageEnglish
Pages (from-to)1358-1365
Number of pages8
JournalStem Cells
Volume27
Issue number6
DOIs
Publication statusPublished - 2009 Jun 1

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Mesenchymal Stromal Cells
Cell Adhesion
Myocardium
Cell Survival
integrin-linked kinase
Ligation
Coronary Vessels
Transplantation
Cell Transplantation
Cell- and Tissue-Based Therapy
Microvessels
Integrins
Caspase 3

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Song, S. W., Chang, W., Song, B. W., Song, H., Lim, S., Kim, H. J., ... Hwang, K. C. (2009). Integrin-linked kinase is required in hypoxic mesenchymal stem cells for strengthening cell adhesion to ischemic myocardium. Stem Cells, 27(6), 1358-1365. https://doi.org/10.1002/stem.47
Song, Suk Won ; Chang, Woochul ; Song, Byeong Wook ; Song, Heesang ; Lim, Soyeon ; Kim, Hye Jung ; Cha, Min Ji ; Choi, Eunju ; Im, Sin Hyeog ; Chang, Byung Chul ; Chung, Namsik ; Jang, Yangsoo ; Hwang, Ki Chul. / Integrin-linked kinase is required in hypoxic mesenchymal stem cells for strengthening cell adhesion to ischemic myocardium. In: Stem Cells. 2009 ; Vol. 27, No. 6. pp. 1358-1365.
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title = "Integrin-linked kinase is required in hypoxic mesenchymal stem cells for strengthening cell adhesion to ischemic myocardium",
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 two-fold 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.",
author = "Song, {Suk Won} and Woochul Chang and Song, {Byeong Wook} and Heesang Song and Soyeon Lim and Kim, {Hye Jung} and Cha, {Min Ji} and Eunju Choi and Im, {Sin Hyeog} and Chang, {Byung Chul} and Namsik Chung and Yangsoo Jang and Hwang, {Ki Chul}",
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Song, SW, Chang, W, Song, BW, Song, H, Lim, S, Kim, HJ, Cha, MJ, Choi, E, Im, SH, Chang, BC, Chung, N, Jang, Y & Hwang, KC 2009, 'Integrin-linked kinase is required in hypoxic mesenchymal stem cells for strengthening cell adhesion to ischemic myocardium', Stem Cells, vol. 27, no. 6, pp. 1358-1365. https://doi.org/10.1002/stem.47

Integrin-linked kinase is required in hypoxic mesenchymal stem cells for strengthening cell adhesion to ischemic myocardium. / Song, Suk Won; Chang, Woochul; Song, Byeong Wook; Song, Heesang; Lim, Soyeon; Kim, Hye Jung; Cha, Min Ji; Choi, Eunju; Im, Sin Hyeog; Chang, Byung Chul; Chung, Namsik; Jang, Yangsoo; Hwang, Ki Chul.

In: Stem Cells, Vol. 27, No. 6, 01.06.2009, p. 1358-1365.

Research output: Contribution to journalArticle

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T1 - Integrin-linked kinase is required in hypoxic mesenchymal stem cells for strengthening cell adhesion to ischemic myocardium

AU - Song, Suk Won

AU - Chang, Woochul

AU - Song, Byeong Wook

AU - Song, Heesang

AU - Lim, Soyeon

AU - Kim, Hye Jung

AU - Cha, Min Ji

AU - Choi, Eunju

AU - Im, Sin Hyeog

AU - Chang, Byung Chul

AU - Chung, Namsik

AU - Jang, Yangsoo

AU - Hwang, Ki Chul

PY - 2009/6/1

Y1 - 2009/6/1

N2 - 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 two-fold 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.

AB - 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 two-fold 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.

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