title: Three-dimensional cell grafting enhances the angiogenic efficacy of human umbilical vein endothelial cells.
abstract: Despite the great potential of cell therapy for ischemic disease, poor cell survival after engraftment in ischemic tissue limits its efficacy. Here we tested a hypothesis that three-dimensionally grafted human umbilical vein endothelial cell (HUVEC) spheroids would exhibit improved angiogenic efficacy following transplantation into mouse ischemic limbs compared with HUVECs prepared by conventional two-dimensional monolayer culture. One day after surgical induction of hindlimb ischemia in athymic mice, HUVECs cultured in monolayer or HUVEC spheroids were transplanted intramuscularly into ischemic limbs. Four weeks after the treatment, in the spheroid HUVEC transplantation group, we observed increased hypoxia-inducible factor-1α expression, decreased apoptosis, and increased HUVEC survival in the ischemic tissue compared with the monolayer HUVEC transplantation group. Transplantation of HUVEC spheroids also resulted in enhanced and prolonged secretion of paracrine factors as well as enhanced expression of factors involved in the recruitment of circulating angiogenic progenitor cells. In summary, transplantation of HUVECs as spheroids enhanced cell survival, increased paracrine factor secretion, and showed a potential as a therapeutic method to treat ischemic tissue damages by promoting angiogenesis.
authors: School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea.
authors: Suk Ho
authors: SH
authors: Bhang
authors: Seahyoung
authors: S
authors: Lee
authors: Tae-Jin
authors: TJ
authors: Lee
authors: Wan-Geun
authors: WG
authors: La
authors: Hee-Seok
authors: HS
authors: Yang
authors: Seung-Woo
authors: SW
authors: Cho
authors: Byung-Soo
authors: BS
authors: Kim
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D002470:Cell Survival; D005109:Extracellular Matrix / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000628:therapy; D019194:Ischemic Preconditioning; D051379:Mice; D018919:Neovascularization, Physiologic; D018874:Spheroids, Cellular / Q000166:cytology / Q000637:transplantation; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D043925:Angiogenesis Inducing Agents