Locally Delivered Growth Factor Enhances the Angiogenic Efficacy of Adipose-Derived Stromal Cells Transplanted to Ischemic Limbs
- 7 May 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in The International Journal of Cell Cloning
- Vol. 27 (8), 1976-1986
- https://doi.org/10.1002/stem.115
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. Disclosure of potential conflicts of interest is found at the end of this article.Keywords
Funding Information
- Korea Health 21 R&D Project funded by the Ministry of Health and Welfare, Republic of Korea (A050082)
- Stem Cell Research Center of the 21st Century Frontier Program funded by the Ministry of Science and Technology, Republic of Korea (SC3220)
- Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A080467)
- National Institutes of Health (NIH RO1-DE016516-03))
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