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 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.

Research highlights
► Transplantation of Flk1+ mGS cells into ischemic heart improved the cardiac systolic function and preserved LV wall thickness.
► Transplantation of Flk1+ mGS cells promoted angiogenesis.
► Transplantation of Flk1+ mGS cells reduced cell senescence in infarcted area and cell death was delayed.
► Flk1+ mGS cells are one of hopeful cell sources for cardiac regeneration therapy.