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Neonatal mouse testis-derived multipotent germline stem cells improve the cardiac function of acute ischemic heart mouse model
Authors:Toru Iwasa  Hiraku Doi  Noritaka Yokoo  Mito Kanatsu-Shinohara  Tatsutoshi Nakahata
Affiliation:a Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
b Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Konoe-cho, Yoshida Sakyo-ku, Kyoto 606-8501, Japan
Abstract: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 4 weeks 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.
Keywords:mGS cells, multipotent germline stem cells   Flk1, fetal liver kinase 1   ES cells, embryonic stem cells   FCS, fetal calf serum   2ME, 2-mercaptoetahnol   LIF, leukemia inhibitory factor   LAD, left anterior descendant coronary artery   LVDd, left ventricular end-diastolic diameter   LVEF, left ventricular ejection fraction   +dP/dt, maximum systolic velocity change   &minus  dP/dt, minimum diastolic velocity change   cTn-I, cardiac troponin-I   TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling   AMI, acute myocardial infarct   iPS cells, induced pluripotent stem cells
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