Abstract 12823: Comparative Angiogenic Activity of Induced Pluripotent Stem Cell Derived From Young and Old Mice
Background: Advanced age is associated with a decreased stem cell activity. Induced pluripotent stem (iPS) cells are a novel stem cell population induced from somatic cells. However, the effect of aging on differentiation capacity of iPS cells into cardiovascular cells has not been fully clarified. Here, we investigated whether young or old mice-derived iPS cells could equally differentiate to vascular progenitor cells, and could regulate vascular responses in vivo employing an ischemic hind limb model.
Methods and Results: iPS cells from mouse embryonic fibroblasts (young) or 21 month- old mouse bone marrow (old) were used in this study. Fetal liver kinase-1 positive (Flk-1+) cells, as a vascular progenitor marker, were induced from young and old mice-derived iPS cells after three to four days of culture.These Flk-1+ cells were sorted and could differentiate into CD31+ endothelial cells and α-SMA+ smooth muscle cells.Tube-like formation by 3D culture was also successfully induced in both young and old mice-derived Flk-1+ cells. Next, hind limb ischemia was surgically induced, and purified Flk-1+ cells were directly injected into ischemic hind limbs of athymic nude mice. Revascularization of the ischemic hind limb was significantly accelerated in mice that were transplanted with Flk-1+ cells from either young or old mice-derived iPS cells compared to control mice that were transplanted with PBS as evaluated by laser Doppler blood flowmetry. The degree of the revascularization was similar between two groups of ischemic mice which were injected with iPS cell-derived Flk-1+ cells from young and old mice. Transplantation of Flk-1+ cells from both young and old mice-derived iPS cells also increased the expression of VEGF mRNA in ischemic tissue compared to controls.
Conclusion: iPS cell-derived Flk-1+ cells could differentiate into vascular progenitor cells, and regulate the angiogenic vascular responses both in vitro and in vivo.These properties of old age-derived iPS cells are largely comparable to those of young age-derived iPS cells, which suggests that the functionality of generated iPS cells themselves were unaffected by aging. Thereby iPS cells could be a potentially useful candidate for therapeutic angiogenesis even in aged subjects.
- © 2011 by American Heart Association, Inc.