Administration of granulocyte colony-stimulating factor after myocardial infarction enhances the recruitment of hematopoietic stem cell-derived myofibroblasts and contributes to cardiac repair

Jun Fujita, Mitsuharu Mori, Hiroshi Kawada, Yasuyo Ieda, Mitsuyo Tsuma, Yumi Matsuzaki, Haruko Kawaguchi, Takashi Yagi, Shinsuke Yuasa, Jin Endo, Tomomitsu Hotta, Satoshi Ogawa, Hideyuki Okano, Ryohei Yozu, Kiyoshi Ando, Keiichi Fukuda

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Abstract

The administration of granulocyte colony-stimulating factor (G-CSF) after myocardial infarction (MI) improves cardiac function and survival rates in mice. It was also reported recently that bone marrow (BM)-derived c-kit+ cells or macrophages in the infarcted heart are associated with improvement of cardiac remodeling and function. These observations prompted us to examine whether BM-derived hematopoietic cells mobilized by G-CSF administration after MI play a beneficial role in the infarct region. A single hematopoietic stem cell from green fluorescent protein (GFP)-transgenic mice was used to reconstitute hematopoiesis in each experimental mouse. MI was then induced, and the mice received G-CSF for 10 days. In the acute phase, a number of GFP + cells showing the elongated morphology were found in the infarcted area. Most of these cells were positive for vimentin and α-smooth muscle actin but negative for CD45, indicating that they were myofibroblasts. The number of these cells was markedly enhanced by G-CSF administration, and the enhanced myofibroblast-rich repair was considered to lead to improvements of cardiac remodeling, function, and survival rate. Next, G-CSF-mobilized monocytes were harvested from the peripheral blood of GFP-transgenic mice and injected intravenously into the infarcted mice. Following this procedure, GFP+ myofibroblasts were observed in the infarcted myocardium. These results indicate that cardiac myofibroblasts are hematopoietic in origin and could arise from monocytes/macrophages. MI leads to the recruitment of monocytes, which differentiate into myofibroblasts in the infarct region. Administration of G-CSF promotes this recruitment and enhances cardiac protection.

Original languageEnglish
Pages (from-to)2750-2759
Number of pages10
JournalStem Cells
Volume25
Issue number11
DOIs
Publication statusPublished - 2007 Nov 1

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Keywords

  • Hematopoietic stem cells
  • Monocytes/macrophages
  • Myocardial infarction granulocyte colony-stimulating factor
  • Myofibroblasts/fibroblasts

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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