Abstract 8572: Enhanced Angiogenesis By Transplantation Of iPS Cell-derived Flk-1+ Cell Sheet Created By A Novel Magnetic Tissue Engineering Method
Background: Therapeutic angiogenesis using cell transplantation represents a novel strategy for severe ischemic diseases, but some patients had poor response to angiogenic cell therapy. Therefore, alternative cell source and cell application strategy have been extensively searched. Induced pluripotent stem cells are expected as one of powerful tools for regenerative medicine. We investigated a therapeutic potential of iPS cell sheet created by a novel magnetite tissue engineering technology for reparative angiogenesis.
Methods and Results: Flk-1+ cells, as a vascular progenitor marker were induced from mouse iPS cells after 5 day of culture. Flk-1+ cells were purified by FACS sorting, and these cells differentiated into CD31+ endothelial and α-SMA+ smooth muscle cells. Sorted Flk-1+ cells incubated with magneticnanoparticle-containing liposomes (MCLs) were cultured. MCL-labeled Flk-1+ cells were mixed with diluted extracellular matrix (ECM) precursor, and a magnet was placed on the reverse side. Magnetized iPS cell-derived Flk-1+ cells formed multilayered cell sheet after 24h incubation period. Nude mice were subjected to unilateral hind limb ischemia and separated into 3 groups. The constructed Flk-1+ cells- or Flk-1−cells- sheet placed on the ischemic adductor muscles using the Alnico magnet before skin closure. For the control group, ECM precursor gel was layered onto the ischemic tissues. Blood flow recovery and the extent of angiogenesis were assessed by a laser doppler blood flowmetry and capillary density. The Flk-1+ cell sheet group had a greater angiogenesis in ischemic tissues compared to the control and Flk-1−cells sheet groups (p<0.05). The angiogenic and tissue-preserving effects of Flk-1+ cell sheets were attributable to an increased expression of VEGF mRNA in ischemic tissues. We did not detect formation of any tumors in Flk-1+ cells, but not in Flk-1−cells, transplanted mice at least until post-operative day 60.
Conclusions: Implantation of iPS cell-derived Flk-1+cells has augmented ischemia-induced angiogenesis. iPS cell-derived Flk-1+ cell sheet created by the novel magnetic nanoparticle-based tissue engineering technology would represent a new modality for therapeutic angiogenesis and tissue regeneration.
- © 2011 by American Heart Association, Inc.