TY - JOUR
T1 - Administration of granulocyte colony-stimulating factor after myocardial infarction enhances the recruitment of hematopoietic stem cell-derived myofibroblasts and contributes to cardiac repair
AU - Fujita, Jun
AU - Mori, Mitsuharu
AU - Kawada, Hiroshi
AU - Ieda, Yasuyo
AU - Tsuma, Mitsuyo
AU - Matsuzaki, Yumi
AU - Kawaguchi, Haruko
AU - Yagi, Takashi
AU - Yuasa, Shinsuke
AU - Endo, Jin
AU - Hotta, Tomomitsu
AU - Ogawa, Satoshi
AU - Okano, Hideyuki
AU - Yozu, Ryohei
AU - Ando, Kiyoshi
AU - Fukuda, Keiichi
PY - 2007/11
Y1 - 2007/11
N2 - 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.
AB - 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.
KW - Hematopoietic stem cells
KW - Monocytes/macrophages
KW - Myocardial infarction granulocyte colony-stimulating factor
KW - Myofibroblasts/fibroblasts
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U2 - 10.1634/stemcells.2007-0275
DO - 10.1634/stemcells.2007-0275
M3 - Article
C2 - 17690181
AN - SCOPUS:36248933189
VL - 25
SP - 2750
EP - 2759
JO - International Journal of Cell Cloning
JF - International Journal of Cell Cloning
SN - 1066-5099
IS - 11
ER -