Administration of granulocyte colony-stimulating factor after myocardial infarction enhances the recruitment of hematopoietic stem cell-derived myofibroblasts and contributes to cardiac repair.
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 alpha-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.
Fujita
Jun
J
Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Mori
Mitsuharu
M
Kawada
Hiroshi
H
Ieda
Yasuyo
Y
Tsuma
Mitsuyo
M
Matsuzaki
Yumi
Y
Kawaguchi
Haruko
H
Yagi
Takashi
T
Yuasa
Shinsuke
S
Endo
Jin
J
Hotta
Tomomitsu
T
Ogawa
Satoshi
S
Okano
Hideyuki
H
Yozu
Ryohei
R
Ando
Kiyoshi
K
Fukuda
Keiichi
K
D000818:Animals; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000000981:diagnostic imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000166:cytology; D011877:Radionuclide Imaging; D012038:Regeneration / Q000502:physiology; D013997:Time Factors
D016179:Granulocyte Colony-Stimulating Factor