title: Comparative angiogenic activities of induced pluripotent stem cells derived from young and old mice.
abstract: Advanced age is associated with decreased stem cell activity. However, the effect of aging on the differentiation capacity of induced pluripotent stem (iPS) cells into cardiovascular cells has not been fully clarified. We investigated whether iPS cells derived from young and old mice are equally capable of differentiating into vascular progenitor cells, and whether these cells regulate vascular responses in vivo. iPS cells from mouse embryonic fibroblasts (young) or 21 month-old mouse bone marrow (old) were used. Fetal liver kinase-1 positive (Flk-1(+)) cells, as a vascular progenitor marker, were induced after 3 to 4 days of culture from iPS cells derived from young and old mice. These Flk-1(+) cells were sorted and shown to differentiate into VE-cadherin(+) endothelial cells and α-SMA(+) smooth muscle cells. Tube-like formation was also successfully induced in both young and old murine Flk-1(+) cells. Next, hindlimb ischemia was surgically induced, and purified Flk-1(+) cells were directly injected into ischemic hindlimbs of nude mice. Revascularization of the ischemic hindlimb was significantly accelerated in mice transplanted with Flk-1(+) cells derived from iPS cells from either young or old mice, as compared to control mice as evaluated by laser Doppler blood flowmetry. The degree of revascularization was similar in the two groups of ischemic mice injected with iPS cell-derived Flk-1(+) cells from young or old mice. Transplantation of Flk-1(+) cells from both young and old murine iPS cells also increased the expression of VEGF, HGF and IGF mRNA in ischemic tissue as compared to controls. iPS cell-derived Flk-1(+) cells differentiated into vascular progenitor cells, and regulated angiogenic vascular responses both in vitro and in vivo. These properties of iPS cells derived from old mice are essentially the same as those of iPS cells from young mice, suggesting the functionality of generated iPS cells themselves to be unaffected by aging.
authors: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Hirohiko
authors: H
authors: Suzuki
authors: Rei
authors: R
authors: Shibata
authors: Tetsutaro
authors: T
authors: Kito
authors: Takashi
authors: T
authors: Yamamoto
authors: Masakazu
authors: M
authors: Ishii
authors: Naomi
authors: N
authors: Nishio
authors: Sachiko
authors: S
authors: Ito
authors: Ken-ichi
authors: K
authors: Isobe
authors: Toyoaki
authors: T
authors: Murohara
mesh_terms: D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D007511:Ischemia / Q000378:metabolism; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D040301:Vascular Endothelial Growth Factor Receptor-2