comparative angiogenic activities of induced pluripotent stem cells derived from young and old mice比较血管生成活动的诱导多能干细胞来自年轻和年老的老鼠.pdf

Comparative Angiogenic Activities of Induced Pluripotent Stem Cells Derived from Young and Old Mice 1 1 1 1 1 2 Hirohiko Suzuki , Rei Shibata *, Tetsutaro Kito , Takashi Yamamoto , Masakazu Ishii , Naomi Nishio , 2 2 1 Sachiko Ito , Ken-ichi Isobe , Toyoaki Murohara * 1 Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan, 2 Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan 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 a-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+