title: Locally delivered growth factor enhances the angiogenic efficacy of adipose-derived stromal cells transplanted to ischemic limbs.
abstract: Ischemia is a potentially fatal medical event that is associated with as many as 30% of all deaths. Stem cell therapy offers significant therapeutic promise, but poor survival following transplantation to ischemic tissue limits its efficacy. Here we demonstrate that nanosphere-mediated growth factor delivery can enhance the survival of transplanted human adipose-derived stromal cells (hADSCs) and secretion of human angiogenic growth factors per cell, and substantially improve therapeutic efficacy of hADSCs. In vitro, in hypoxic (1% oxygen) and serum-deprived conditions that simulate in vivo ischemia, fibroblast growth factor-2 (FGF2) significantly reduced hADSC apoptosis and enhanced angiogenic growth factor secretion. In vivo, hADSCs delivered intramuscularly into ischemic hind limbs in combination with FGF2 resulted in significant improvements in limb survival and blood perfusion, as well as survival of the transplanted hADSCs and secretion of human angiogenic growth factors (i.e., vascular endothelial growth factor, hepatocyte growth factor, and FGF2). Interestingly, the majority of transplanted hADSCs were localized adjacent to the microvessels rather than being incorporated into them, suggesting that their major contribution to angiogenesis might be to increase paracrine secretion of angiogenic growth factors. This study demonstrates the potential of hADSCs in combination with growth factors for use in the treatment of ischemia.
authors: Department of Bioengineering, College of Medicine, Hanyang University, Seoul, Korea. bskim@hanyang.ac.kr
authors: Suk Ho
authors: SH
authors: Bhang
authors: Seung-Woo
authors: SW
authors: Cho
authors: Jae Min
authors: JM
authors: Lim
authors: Jin Muk
authors: JM
authors: Kang
authors: Tae-Jin
authors: TJ
authors: Lee
authors: Hee Seok
authors: HS
authors: Yang
authors: Young Soo
authors: YS
authors: Song
authors: Moon Hyang
authors: MH
authors: Park
authors: Hyo-Soo
authors: HS
authors: Kim
authors: Kyung-Jong
authors: KJ
authors: Yoo
authors: Yangsoo
authors: Y
authors: Jang
authors: Robert
authors: R
authors: Langer
authors: Daniel G
authors: DG
authors: Anderson
authors: Byung-Soo
authors: BS
authors: Kim
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D050154:Adiposity / Q000235:genetics; D043925:Angiogenesis Inducing Agents; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D005455:Fluorescent Antibody Technique; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000601:surgery / Q000628:therapy*; D023821:Limb Salvage; D051379:Mice; D008819:Mice, Nude; D017154:Stromal Cells / Q000637:transplantation*
chemical_list: D043925:Angiogenesis Inducing Agents; D042501:Angiogenic Proteins; D016222:Fibroblast Growth Factor 2