Locally delivered growth factor enhances the angiogenic efficacy of adipose-derived stromal cells transplanted to ischemic limbs

Suk Ho Bhang, Seung Woo Cho, Jae Min Lim, Jin Muk Kang, Tae Jin Lee, Hee Seok Yang, Young Soo Song, Moon Hyang Park, Hyo Soo Kim, Kyung Jong Yoo, Yangsoo Jang, Robert Langer, Daniel G. Anderson, Byung Soo Kim

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1976-1986
Number of pages11
JournalStem Cells
Volume27
Issue number8
DOIs
Publication statusPublished - 2009 Aug 1

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Stromal Cells
Intercellular Signaling Peptides and Proteins
Extremities
Angiogenesis Inducing Agents
Fibroblast Growth Factor 2
Ischemia
Survival
Nanospheres
Hepatocyte Growth Factor
Cell- and Tissue-Based Therapy
Microvessels
Vascular Endothelial Growth Factor A
Stem Cells
Therapeutics
Perfusion
Transplantation
Apoptosis
Oxygen
Serum

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Bhang, Suk Ho ; Cho, Seung Woo ; Lim, Jae Min ; Kang, Jin Muk ; Lee, Tae Jin ; Yang, Hee Seok ; Song, Young Soo ; Park, Moon Hyang ; Kim, Hyo Soo ; Yoo, Kyung Jong ; Jang, Yangsoo ; Langer, Robert ; Anderson, Daniel G. ; Kim, Byung Soo. / Locally delivered growth factor enhances the angiogenic efficacy of adipose-derived stromal cells transplanted to ischemic limbs. In: Stem Cells. 2009 ; Vol. 27, No. 8. pp. 1976-1986.
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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.",
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Bhang, SH, Cho, SW, Lim, JM, Kang, JM, Lee, TJ, Yang, HS, Song, YS, Park, MH, Kim, HS, Yoo, KJ, Jang, Y, Langer, R, Anderson, DG & Kim, BS 2009, 'Locally delivered growth factor enhances the angiogenic efficacy of adipose-derived stromal cells transplanted to ischemic limbs', Stem Cells, vol. 27, no. 8, pp. 1976-1986. https://doi.org/10.1002/stem.115

Locally delivered growth factor enhances the angiogenic efficacy of adipose-derived stromal cells transplanted to ischemic limbs. / Bhang, Suk Ho; Cho, Seung Woo; Lim, Jae Min; Kang, Jin Muk; Lee, Tae Jin; Yang, Hee Seok; Song, Young Soo; Park, Moon Hyang; Kim, Hyo Soo; Yoo, Kyung Jong; Jang, Yangsoo; Langer, Robert; Anderson, Daniel G.; Kim, Byung Soo.

In: Stem Cells, Vol. 27, No. 8, 01.08.2009, p. 1976-1986.

Research output: Contribution to journalArticle

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T1 - Locally delivered growth factor enhances the angiogenic efficacy of adipose-derived stromal cells transplanted to ischemic limbs

AU - Bhang, Suk Ho

AU - Cho, Seung Woo

AU - Lim, Jae Min

AU - Kang, Jin Muk

AU - Lee, Tae Jin

AU - Yang, Hee Seok

AU - Song, Young Soo

AU - Park, Moon Hyang

AU - Kim, Hyo Soo

AU - Yoo, Kyung Jong

AU - Jang, Yangsoo

AU - Langer, Robert

AU - Anderson, Daniel G.

AU - Kim, Byung Soo

PY - 2009/8/1

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N2 - 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.

AB - 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.

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