Increased angiogenesis and improved left ventricular function after transplantation of myoblasts lacking the MyoD gene into infarcted myocardium

Yasuhiro Nakamura, Yoko Asakura, Bryan A. Piras, Hiroyuki Hirai, Christopher T. Tastad, Mayank Verma, Amanda J. Christ, Jianyi Zhang, Takanori Yamazaki, Minoru Yoshiyama, Atsushi Asakura*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Skeletal myoblast transplantation has therapeutic potential for repairing damaged heart. However, the optimal conditions for this transplantation are still unclear. Recently, we demonstrated that satellite cell-derived myoblasts lacking the MyoD gene (MyoD-/-), a master transcription factor for skeletal muscle myogenesis, display increased survival and engraftment compared to wild-type controls following transplantation into murine skeletal muscle. In this study, we compare cell survival between wild-type and MyoD-/- myoblasts after transplantation into infarcted heart. We demonstrate that MyoD-/- myoblasts display greater resistance to hypoxia, engraft with higher efficacy, and show a larger improvement in ejection fraction than wild-type controls. Following transplantation, the majority of MyoD-/- and wild-type myoblasts form skeletal muscle fibers while cardiomyocytes do not. Importantly, the transplantation of MyoD-/- myoblasts induces a high degree of angiogenesis in the area of injury. DNA microarray data demonstrate that paracrine angiogenic factors, such as stromal cell-derived factor-1 (SDF-1) and placental growth factor (PlGF), are up-regulated in MyoD-/- myoblasts. In addition, over-expression and gene knockdown experiments demonstrate that MyoD negatively regulates gene expression of these angiogenic factors. These results indicate that MyoD-/- myoblasts impart beneficial effects after transplantation into an infarcted heart, potentially due to the secretion of paracrine angiogenic factors and enhanced angiogenesis in the area of injury. Therefore, our data provide evidence that a genetically engineered myoblast cell type with suppressed MyoD function is useful for therapeutic stem cell transplantation.

Original languageEnglish (US)
Article numbere41736
JournalPloS one
Volume7
Issue number7
DOIs
StatePublished - Jul 25 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Nakamura, Y., Asakura, Y., Piras, B. A., Hirai, H., Tastad, C. T., Verma, M., Christ, A. J., Zhang, J., Yamazaki, T., Yoshiyama, M., & Asakura, A. (2012). Increased angiogenesis and improved left ventricular function after transplantation of myoblasts lacking the MyoD gene into infarcted myocardium. PloS one, 7(7), [e41736]. https://doi.org/10.1371/journal.pone.0041736