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Locally Delivered Growth Factor Enhances the Angiogenic Efficacy of Adipose-Derived Stromal Cells Transplanted to Ischemic Limbs

Cited 58 time in Web of Science Cited 61 time in Scopus
Authors
Bhang, Suk Ho; Cho, Seung-Woo; Lim, Jae Min; Kang, Jin Muk; Yang, Hee Seok; Park, Moon Hyang; Yoo, Kyung-Jong; Langer, Robert; Kim, Byung-Soo; Anderson, Daniel G.; Jang, Yangsoo; Kim, Hyo-Soo; Song, Young Soo; Lee, Tae-Jin
Issue Date
2009-08
Publisher
WILEY-BLACKWELL
Citation
STEM CELLS; Vol.27 8; 1976-1986
Keywords
Human adipose-derived stromal cellParacrine effectTherapeutic angiogenesisHind limb ischemiaLocal deliveryFibroblast growth factor-2
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 micro-vessels 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. STEM CELLS 2009;27:1976-1986
ISSN
1066-5099
Language
English
URI
http://hdl.handle.net/10371/76400
DOI
https://doi.org/10.1002/stem.115
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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