Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction.
Bone marrow (BM) cells are reported to contribute to the process of regeneration following myocardial infarction. However, the responsible BM cells have not been fully identified. Here, we used 2 independent clonal studies to determine the origin of bone marrow (BM)-derived cardiomyocytes. First, we transplanted single CD34(-) c-kit(+)Sca-1(+) lineage(-) side population (CD34(-)KSL-SP) cells or whole BM cells from mice ubiquitously expressing enhanced green fluorescent protein (EGFP) into lethally irradiated mice, induced myocardial infarction (MI), and treated the animals with granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells to the damaged myocardium. At 8 weeks after MI, from 100 specimens we counted only 3 EGFP(+) actinin(+) cells in myocardium of CD34(-) KSL-SP cells in mice that received transplants, but more than 5000 EGFP(+) actinin(+) cells in whole BM cell in mice that received transplants, suggesting that most of EGFP(+) actinin(+) cells were derived from nonhematopoietic BM cells. Next, clonally purified nonhematopoietic mesenchymal stem cells (MSCs), cardiomyogenic (CMG) cells, that expressed EGFP in the cardiomyocyte-specific manner were transplanted directly into BM of lethally irradiated mice, MI was induced, and they were treated with G-CSF. EGFP(+) actinin(+) cells were observed in the ischemic myocardium, indicating that CMG cells had been mobilized and differentiated into cardiomyocytes. Together, these results suggest that the origin of the vast majority of BM-derived cardiomyocytes is MSCs.
Kawada
Hiroshi
H
Division of Hematology, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Fujita
Jun
J
Kinjo
Kentaro
K
Matsuzaki
Yumi
Y
Tsuma
Mitsuyo
M
Miyatake
Hiroko
H
Muguruma
Yukari
Y
Tsuboi
Kosuke
K
Itabashi
Yuji
Y
Ikeda
Yasuo
Y
Ogawa
Satoshi
S
Okano
Hideyuki
H
Hotta
Tomomitsu
T
Ando
Kiyoshi
K
Fukuda
Keiichi
K
D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D019070:Cell Lineage; D002633:Chemotaxis; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D049452:Green Fluorescent Proteins / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology* / Q000502:physiology*; D012038:Regeneration
D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins