Impact of myocardial infarct proteins and oscillating pressure on the differentiation of mesenchymal stem cells: Effect of acute myocardial infarction on stem cell differentiation

Sung A. Chang, Ju Lee Eun, Hyun Jae Kang, Shu Ying Zhang, Ji Hyun Kim, Lian Li, Seock Won Youn, Choon Soo Lee, Keum Hyun Kim, Joo Yun Won, Jong Woo Sohn, Kyung Woo Park, Hyun Jai Cho, Sung Eun Yang, Il Oh Won, Sun Yang Yoon, Won Kyung Ho, Young Bae Park, Hyo Soo Kim

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Stem cell transplantation in acute myocardial infarction (AMI) has emerged as a promising therapeutic option. We evaluated the impact of AMI on mesenchymal stem cell (MSC) differentiation into cardiomyocyte lineage. Cord blood-derived human MSCs were exposed to in vitro conditions simulating in vivo environments of the beating heart with acute ischemia, as follows: (a) myocardial proteins or serum obtained from sham-operated rats, and (b) myocardial proteins or serum from AMI rats, with or without application of oscillating pressure. Expression of cardiac-specific markers on MSCs was greatly induced by the infarcted myocardial proteins, compared with the normal proteins. It was also induced by application of oscillating pressure to MSCs. Treatment of MSCs with infarcted myocardial proteins and oscillating pressure greatly augmented expression of cardiac-specific genes. Such expression was blocked by inhibitor of transforming growth factor β 1 (TGF-β 1 ) or bone morphogenetic protein-2 (BMP-2). In vitro cellular and electrophysiologic experiments showed that these differentiated MSCs expressing cardiomyocytespecific markers were able to make a coupling with cardiomyocytes but not to selfbeat. The pathophysiologic significance of in vitro results was confirmed using the rat AMI model. The protein amount of TGF-β 1 and BMP-2 in myocardium of AMI was significantly higher than that in normal myocardium. When MSCs were transplanted to the heart and analyzed 8 weeks later, they expressed cardiomyocyte-specific markers, leading to improved cardiac function. These in vitro and in vivo results suggest that infarctrelated biological and physical factors in AMI induce commitment of MSCs to cardiomyocyte-like cells through TGF-β/BMP-2 pathways.

Original languageEnglish (US)
Pages (from-to)1901-1912
Number of pages12
JournalStem Cells
Volume26
Issue number7
DOIs
StatePublished - Jul 1 2008

Keywords

  • Acute myocardial infarction
  • Cardiomyocytes
  • Differentiation
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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    Chang, S. A., Eun, J. L., Kang, H. J., Zhang, S. Y., Kim, J. H., Li, L., Youn, S. W., Lee, C. S., Kim, K. H., Won, J. Y., Sohn, J. W., Park, K. W., Cho, H. J., Yang, S. E., Won, I. O., Yoon, S. Y., Ho, W. K., Park, Y. B., & Kim, H. S. (2008). Impact of myocardial infarct proteins and oscillating pressure on the differentiation of mesenchymal stem cells: Effect of acute myocardial infarction on stem cell differentiation. Stem Cells, 26(7), 1901-1912. https://doi.org/10.1634/stemcells.2007-0708