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

Heesang Song, Kihwan Kwon, Soyeon Lim, Seok Min 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 journalArticlepeer-review

102 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 Ca2+ 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
Publication statusPublished - 2005

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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