Neonatal mouse testis-derived multipotent germline stem cells improve the cardiac function of acute ischemic heart mouse model.
Multipotent germline stem (mGS) cells have been established from neonatal mouse testes. We previously reported that undifferentiated mGS cells are phenotypically similar to embryonic stem cells and that fetal liver kinase 1 (Flk1)(+) mGS cells have a similar potential to differentiate into cardiomyocytes and endothelial cells compared with Flk1(+) embryonic stem cells. Here, we transplanted these Flk1(+) mGS cells into an ischemic heart failure mouse model to evaluate the improvement in cardiac function. Significant increase in left ventricular wall thickness of the infarct area, left ventricular ejection fraction and left ventricular maximum systolic velocity was observed 4weeks after when sorted Flk1(+) mGS cells were transplanted directly into the hearts of the acute ischemic model mice. Although the number of cardiomyocytes derived from Flk1(+) mGS cells were too small to account for the improvement in cardiac function but angiogenesis around ischemic area was enhanced in the Flk1(+) mGS cells transplanted group than the control group and senescence was also remarkably diminished in the early phase of ischemia according to β-galactosidase staining assay. In conclusion, Flk1(+) mGS cell transplantation can improve the cardiac function of ischemic hearts by promoting angiogenesis and by delaying host cell death via senescence.
Iwasa
Toru
T
Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Baba
Shiro
S
Doi
Hiraku
H
Kaichi
Shinji
S
Yokoo
Noritaka
N
Mima
Takahiro
T
Kanatsu-Shinohara
Mito
M
Shinohara
Takashi
T
Nakahata
Tatsutoshi
T
Heike
Toshio
T
D000818:Animals; D002454:Cell Differentiation; D016922:Cellular Senescence; D004195:Disease Models, Animal; D005854:Germ Cells / Q000166:cytology* / Q000201:enzymology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D039902:Multipotent Stem Cells / Q000201:enzymology / Q000637:transplantation*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology*; D013737:Testis / Q000166:cytology* / Q000201:enzymology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
D040301:Vascular Endothelial Growth Factor Receptor-2