Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions

Heesang Song, Kihwan Kwon, Soyeon Lim, seokmin kang, Young Guk Ko, Zheng Zhe Xu, Ji Hyung Chung, Byung Soo Kim, Hakbae Lee, Boyoung Joung, Sungha Park, Donghoon Choi, Yangsoo Jang, Nam Sik Chung, Kyung Jong Yoo, Ki Chul Hwang

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. To reduce cell loss after transplantation, we introduced the fibroblast growth factor-2 (FGF-2) gene ex vivo before transplantation. The isolated MSCs produced colonies with a fibroblast-like morphology in 2 weeks; over 95% expressed CD71, and 28% expressed the cardiomyocyte-specific transcription factor, Nkx2.5, as well as α-skeletal actin, Nkx2.5, and GATA4. In hypoxic culture, the FGF-2-transfected MSCs (FGF-2-MSCs) secreted increased levels of FGF-2 and displayed a threefold increase in viability, as well as increased expression of the anti-apoptotic gene, Bcl2, and reduced DNA laddering. They had functional adrenergic receptors, like cardiomyocytes, and exposure to norepinephrine led to phosphorylation of ERK1/2. Viable cells persisted 4 weeks after implantation of 5.0 × 10 5 FGF-2-MSCs into infarcted myocardia. Expression of cardiac troponin T (CTn T) and a voltage-gated Ca 2+ channel (CaV2.1) increased, and new blood vessels formed. These data suggest that genetic modification of MSCs before transplantation could be useful for treating myocardial infarction and end-stage cardiac failure.

Original languageEnglish
Pages (from-to)402-407
Number of pages6
JournalMolecules and cells
Volume19
Issue number3
DOIs
Publication statusPublished - 2005 Dec 1

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Fibroblast Growth Factor 2
Mesenchymal Stromal Cells
Transfection
Transplantation
Cardiac Myocytes
Genes
Mesenchymal Stem Cell Transplantation
Troponin T
Adrenergic Receptors
Blood Vessels
Actins
Myocardium
Norepinephrine
Transcription Factors
Heart Failure
Fibroblasts
Bone Marrow
Myocardial Infarction
Phosphorylation
DNA

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Song, Heesang ; Kwon, Kihwan ; Lim, Soyeon ; kang, seokmin ; Ko, Young Guk ; Xu, Zheng Zhe ; Chung, Ji Hyung ; Kim, Byung Soo ; Lee, Hakbae ; Joung, Boyoung ; Park, Sungha ; Choi, Donghoon ; Jang, Yangsoo ; Chung, Nam Sik ; Yoo, Kyung Jong ; Hwang, Ki Chul. / Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions. In: Molecules and cells. 2005 ; Vol. 19, No. 3. pp. 402-407.
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abstract = "Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. To reduce cell loss after transplantation, we introduced the fibroblast growth factor-2 (FGF-2) gene ex vivo before transplantation. The isolated MSCs produced colonies with a fibroblast-like morphology in 2 weeks; over 95{\%} expressed CD71, and 28{\%} expressed the cardiomyocyte-specific transcription factor, Nkx2.5, as well as α-skeletal actin, Nkx2.5, and GATA4. In hypoxic culture, the FGF-2-transfected MSCs (FGF-2-MSCs) secreted increased levels of FGF-2 and displayed a threefold increase in viability, as well as increased expression of the anti-apoptotic gene, Bcl2, and reduced DNA laddering. They had functional adrenergic receptors, like cardiomyocytes, and exposure to norepinephrine led to phosphorylation of ERK1/2. Viable cells persisted 4 weeks after implantation of 5.0 × 10 5 FGF-2-MSCs into infarcted myocardia. Expression of cardiac troponin T (CTn T) and a voltage-gated Ca 2+ channel (CaV2.1) increased, and new blood vessels formed. These data suggest that genetic modification of MSCs before transplantation could be useful for treating myocardial infarction and end-stage cardiac failure.",
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Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions. / Song, Heesang; Kwon, Kihwan; Lim, Soyeon; kang, seokmin; Ko, Young Guk; Xu, Zheng Zhe; Chung, Ji Hyung; Kim, Byung Soo; Lee, Hakbae; Joung, Boyoung; Park, Sungha; Choi, Donghoon; Jang, Yangsoo; Chung, Nam Sik; Yoo, Kyung Jong; Hwang, Ki Chul.

In: Molecules and cells, Vol. 19, No. 3, 01.12.2005, p. 402-407.

Research output: Contribution to journalArticle

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AU - Song, Heesang

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AU - Lim, Soyeon

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AU - Ko, Young Guk

AU - Xu, Zheng Zhe

AU - Chung, Ji Hyung

AU - Kim, Byung Soo

AU - Lee, Hakbae

AU - Joung, Boyoung

AU - Park, Sungha

AU - Choi, Donghoon

AU - Jang, Yangsoo

AU - Chung, Nam Sik

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AU - Hwang, Ki Chul

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AB - Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. To reduce cell loss after transplantation, we introduced the fibroblast growth factor-2 (FGF-2) gene ex vivo before transplantation. The isolated MSCs produced colonies with a fibroblast-like morphology in 2 weeks; over 95% expressed CD71, and 28% expressed the cardiomyocyte-specific transcription factor, Nkx2.5, as well as α-skeletal actin, Nkx2.5, and GATA4. In hypoxic culture, the FGF-2-transfected MSCs (FGF-2-MSCs) secreted increased levels of FGF-2 and displayed a threefold increase in viability, as well as increased expression of the anti-apoptotic gene, Bcl2, and reduced DNA laddering. They had functional adrenergic receptors, like cardiomyocytes, and exposure to norepinephrine led to phosphorylation of ERK1/2. Viable cells persisted 4 weeks after implantation of 5.0 × 10 5 FGF-2-MSCs into infarcted myocardia. Expression of cardiac troponin T (CTn T) and a voltage-gated Ca 2+ channel (CaV2.1) increased, and new blood vessels formed. These data suggest that genetic modification of MSCs before transplantation could be useful for treating myocardial infarction and end-stage cardiac failure.

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