Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

Transfection of Mesenchymal Stem Cells with the FGF-2 Gene Improves Their Survival Under Hypoxic Conditions

  • Song, Heesang (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine) ;
  • Kwon, Kihwan (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine) ;
  • Lim, Soyeon (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine) ;
  • Kang, Seok-Min (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine) ;
  • Ko, Young-Guk (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine) ;
  • Xu, ZhengZhe (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine) ;
  • Chung, Ji Hyung (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine) ;
  • Kim, Byung-Soo (Department of Chemical Engineering, Hanyang University) ;
  • Lee, Hakbae (Department of Applied Statistics, Yonsei University) ;
  • Joung, Boyoung (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine) ;
  • Park, Sungha (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine) ;
  • Choi, Donghoon (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine) ;
  • Jang, Yangsoo (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine) ;
  • Chung, Nam-Sik (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine) ;
  • Yoo, Kyung-Jong (Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine) ;
  • Hwang, Ki-Chul (Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Cardiology Division, Yonsei University College of Medicine)
  • Received : 2005.01.28
  • Accepted : 2005.03.18
  • Published : 2005.06.30
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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 ${\alpha}$-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 $5.0{\times}10^5$ 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.

Keywords

Acknowledgement

Supported by : Ministry of Health & Welfare

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