Flk1+ cardiac stem/progenitor cells derived from embryonic stem cells improve cardiac function in a dilated cardiomyopathy mouse model

Shiro Baba, Toshio Heike, Momoko Yoshimoto, Katsutsugu Umeda, Hiraku Doi, Toru Iwasa, Xue Lin, Satoshi Matsuoka, Masashi Komeda, Tatsutoshi Nakahata

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Objectives: Flk1+ cells derived from embryonic stem (ES) cells are known to differentiate into mesodermal lineages such as hematopoietic and endothelial cells. Here we demonstrate that they can develop into cardiomyocytes that support functional recovery in a dilated cardiomyopathy (DCM) C57/BL6 mouse model. Methods: Flk1+ and Flk1- cells were sorted at day 4 of differentiation, and cardiomyogenesis was assessed in vitro. Next, we transplanted these cells into the hearts of cardiomyopathy mice to assess improvement in cardiac function. Results: Flk1+ cells, but not Flk1- cells, isolated on day 4 after differentiation were efficiently converted into contractile cardiomyocytes. RT-PCR analysis and immunohistological assays demonstrated that contractile cells derived from Flk1+ cells in vitro expressed mature cardiac markers on day 10 after differentiation. Transplantation of sorted Flk1+ cells into DCM model mouse hearts improved cardiac function, as determined by echocardiography and cardiac catheterization. The in vivo differentiated Flk1+ cells expressed cardiac markers and had gap junctions, as demonstrated by immunohistochemistry. Furthermore, these cells generated ventricular type action potentials similar to those of adult ventricle. Conclusion: These results indicate that Flk1 is a good marker for sorting cardiac stem/progenitor cells which can differentiate into mature cardiomyocytes both in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)119-131
Number of pages13
JournalCardiovascular research
Volume76
Issue number1
DOIs
StatePublished - Oct 1 2007

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Keywords

  • Cardiomyopathy
  • Cell culture/isolation
  • Cell differentiation
  • Cell therapy

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Baba, S., Heike, T., Yoshimoto, M., Umeda, K., Doi, H., Iwasa, T., Lin, X., Matsuoka, S., Komeda, M., & Nakahata, T. (2007). Flk1+ cardiac stem/progenitor cells derived from embryonic stem cells improve cardiac function in a dilated cardiomyopathy mouse model. Cardiovascular research, 76(1), 119-131. https://doi.org/10.1016/j.cardiores.2007.05.013