Neural crest-derived stem cells migrate and differentiate into cardiomyocytes after myocardial infarction

Yuichi Tamura, Keisuke Matsumura, Motoaki Sano, Hidenori Tabata, Kensuke Kimura, Masaki Ieda, Takahide Arai, Yohei Ohno, Hideaki Kanazawa, Shinsuke Yuasa, Ruri Kaneda, Shinji Makino, Kazunori Nakajima, Hideyuki Okano, Keiichi Fukuda

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Objective-: We recently demonstrated that primitive neural crest-derived (NC) cells migrate from the cardiac neural crest during embryonic development and remain in the heart as dormant stem cells, with the capacity to differentiate into various cell types, including cardiomyocytes. Here, we examined the migration and differentiation potential of these cells on myocardial infarction (MI). Methods and Results-: We obtained double-transgenic mice by crossing protein-0 promoter-Cre mice with Floxed-enhanced green fluorescent protein mice, in which the NC cells express enhanced green fluorescent protein. In the neonatal heart, NC stem cells (NCSCs) were localized predominantly in the outflow tract, but they were also distributed in a gradient from base to apex throughout the ventricular myocardium. Time-lapse video analysis revealed that the NCSCs were migratory. Some NCSCs persisted in the adult heart. On MI, NCSCs accumulated at the ischemic border zone area (BZA), which expresses monocyte chemoattractant protein-1 (MCP-1). Ex vivo cell migration assays demonstrated that MCP-1 induced NCSC migration and that this chemotactic effect was significantly depressed by an anti-MCP-1 antibody. Small NC cardiomyocytes first appeared in the BZA 2 weeks post-MI and gradually increased in number thereafter. Conclusion-: These results suggested that NCSCs migrate into the BZA via MCP-1/CCR2 signaling and contribute to the provision of cardiomyocytes for cardiac regeneration after MI.

Original languageEnglish
Pages (from-to)582-589
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number3
DOIs
Publication statusPublished - 2011 Mar

Fingerprint

Neural Crest
Cardiac Myocytes
Stem Cells
Myocardial Infarction
Chemokine CCL2
Cell Migration Assays
Transgenic Mice
Embryonic Development
Cell Movement
Regeneration
Cell Differentiation
Myocardium
Antibodies
Proteins

Keywords

  • biology, developmental
  • cardiac regeneration
  • cytokines
  • ischemic heart disease
  • molecular biology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Neural crest-derived stem cells migrate and differentiate into cardiomyocytes after myocardial infarction. / Tamura, Yuichi; Matsumura, Keisuke; Sano, Motoaki; Tabata, Hidenori; Kimura, Kensuke; Ieda, Masaki; Arai, Takahide; Ohno, Yohei; Kanazawa, Hideaki; Yuasa, Shinsuke; Kaneda, Ruri; Makino, Shinji; Nakajima, Kazunori; Okano, Hideyuki; Fukuda, Keiichi.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 31, No. 3, 03.2011, p. 582-589.

Research output: Contribution to journalArticle

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