Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells

Jalees Rehman, Dmitry Traktuev, Jingling Li, Stephanie Merfeld-Clauss, Constance J. Temm-Grove, Jason E. Bovenkerk, Carrie L. Pell, Brian H. Johnstone, Robert Considine, Keith L. March

Research output: Contribution to journalArticle

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Abstract

Background-The delivery of autologous cells to increase angiogenesis is emerging as a treatment option for patients with cardiovascular disease but may be limited by the accessibility of sufficient cell numbers. The beneficial effects of delivered cells appear to be related to their pluripotency and ability to secrete growth factors. We examined nonadipocyte stromal cells from human subcutaneous fat as a novel source of therapeutic cells. Methods and Results-Adipose stromal cells (ASCs) were isolated from human subcutaneous adipose tissue and characterized by flow cytometry. ASCs secreted 1203±254 pg of vascular endothelial growth factor (VEGF) per 10 6 cells, 12 280±2944 pg of hepatocyte growth factor per 106 cells, and 1247±346 pg of transforming growth factor-β per 106 cells. When ASCs were cultured in hypoxic conditions, VEGF secretion increased 5-fold to 5980±1066 pg/10 6 cells (P=0.0016). The secretion of VEGF could also be augmented 200-fold by transfection of ASCs with a plasmid encoding VEGF (P<0.05). Conditioned media obtained from hypoxic ASCs significantly increased endothelial cell growth (P<0.001) and reduced endothelial cell apoptosis (P<0.05). Nude mice with ischemic hindlimbs demonstrated marked perfusion improvement when treated with human ASCs (P<0.05). Conclusions-Our experiments delineate the angiogenic and antiapoptotic potential of easily accessible subcutaneous adipose stromal cells by demonstrating the secretion of multiple potentially synergistic proangiogenic growth factors. These findings suggest that autologous delivery of either native or transduced subcutaneous ASCs, which are regulated by hypoxia, may be a novel therapeutic option to enhance angiogenesis or achieve cardiovascular protection.

Original languageEnglish
Pages (from-to)1292-1298
Number of pages7
JournalCirculation
Volume109
Issue number10
DOIs
StatePublished - Mar 16 2004

Fingerprint

Angiogenesis Inducing Agents
Stromal Cells
Vascular Endothelial Growth Factor A
Subcutaneous Fat
Intercellular Signaling Peptides and Proteins
Endothelial Cells
Hepatocyte Growth Factor
Transforming Growth Factors
Hindlimb
Conditioned Culture Medium
Nude Mice
Transfection
Flow Cytometry
Plasmids
Cardiovascular Diseases
Therapeutics
Perfusion
Cell Count
Apoptosis
Growth

Keywords

  • Angiogenesis
  • Cells
  • Endothelium

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Rehman, J., Traktuev, D., Li, J., Merfeld-Clauss, S., Temm-Grove, C. J., Bovenkerk, J. E., ... March, K. L. (2004). Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells. Circulation, 109(10), 1292-1298. https://doi.org/10.1161/01.CIR.0000121425.42966.F1

Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells. / Rehman, Jalees; Traktuev, Dmitry; Li, Jingling; Merfeld-Clauss, Stephanie; Temm-Grove, Constance J.; Bovenkerk, Jason E.; Pell, Carrie L.; Johnstone, Brian H.; Considine, Robert; March, Keith L.

In: Circulation, Vol. 109, No. 10, 16.03.2004, p. 1292-1298.

Research output: Contribution to journalArticle

Rehman, J, Traktuev, D, Li, J, Merfeld-Clauss, S, Temm-Grove, CJ, Bovenkerk, JE, Pell, CL, Johnstone, BH, Considine, R & March, KL 2004, 'Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells', Circulation, vol. 109, no. 10, pp. 1292-1298. https://doi.org/10.1161/01.CIR.0000121425.42966.F1
Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE et al. Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells. Circulation. 2004 Mar 16;109(10):1292-1298. https://doi.org/10.1161/01.CIR.0000121425.42966.F1
Rehman, Jalees ; Traktuev, Dmitry ; Li, Jingling ; Merfeld-Clauss, Stephanie ; Temm-Grove, Constance J. ; Bovenkerk, Jason E. ; Pell, Carrie L. ; Johnstone, Brian H. ; Considine, Robert ; March, Keith L. / Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells. In: Circulation. 2004 ; Vol. 109, No. 10. pp. 1292-1298.
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abstract = "Background-The delivery of autologous cells to increase angiogenesis is emerging as a treatment option for patients with cardiovascular disease but may be limited by the accessibility of sufficient cell numbers. The beneficial effects of delivered cells appear to be related to their pluripotency and ability to secrete growth factors. We examined nonadipocyte stromal cells from human subcutaneous fat as a novel source of therapeutic cells. Methods and Results-Adipose stromal cells (ASCs) were isolated from human subcutaneous adipose tissue and characterized by flow cytometry. ASCs secreted 1203±254 pg of vascular endothelial growth factor (VEGF) per 10 6 cells, 12 280±2944 pg of hepatocyte growth factor per 106 cells, and 1247±346 pg of transforming growth factor-β per 106 cells. When ASCs were cultured in hypoxic conditions, VEGF secretion increased 5-fold to 5980±1066 pg/10 6 cells (P=0.0016). The secretion of VEGF could also be augmented 200-fold by transfection of ASCs with a plasmid encoding VEGF (P<0.05). Conditioned media obtained from hypoxic ASCs significantly increased endothelial cell growth (P<0.001) and reduced endothelial cell apoptosis (P<0.05). Nude mice with ischemic hindlimbs demonstrated marked perfusion improvement when treated with human ASCs (P<0.05). Conclusions-Our experiments delineate the angiogenic and antiapoptotic potential of easily accessible subcutaneous adipose stromal cells by demonstrating the secretion of multiple potentially synergistic proangiogenic growth factors. These findings suggest that autologous delivery of either native or transduced subcutaneous ASCs, which are regulated by hypoxia, may be a novel therapeutic option to enhance angiogenesis or achieve cardiovascular protection.",
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AU - Bovenkerk, Jason E.

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AU - Considine, Robert

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N2 - Background-The delivery of autologous cells to increase angiogenesis is emerging as a treatment option for patients with cardiovascular disease but may be limited by the accessibility of sufficient cell numbers. The beneficial effects of delivered cells appear to be related to their pluripotency and ability to secrete growth factors. We examined nonadipocyte stromal cells from human subcutaneous fat as a novel source of therapeutic cells. Methods and Results-Adipose stromal cells (ASCs) were isolated from human subcutaneous adipose tissue and characterized by flow cytometry. ASCs secreted 1203±254 pg of vascular endothelial growth factor (VEGF) per 10 6 cells, 12 280±2944 pg of hepatocyte growth factor per 106 cells, and 1247±346 pg of transforming growth factor-β per 106 cells. When ASCs were cultured in hypoxic conditions, VEGF secretion increased 5-fold to 5980±1066 pg/10 6 cells (P=0.0016). The secretion of VEGF could also be augmented 200-fold by transfection of ASCs with a plasmid encoding VEGF (P<0.05). Conditioned media obtained from hypoxic ASCs significantly increased endothelial cell growth (P<0.001) and reduced endothelial cell apoptosis (P<0.05). Nude mice with ischemic hindlimbs demonstrated marked perfusion improvement when treated with human ASCs (P<0.05). Conclusions-Our experiments delineate the angiogenic and antiapoptotic potential of easily accessible subcutaneous adipose stromal cells by demonstrating the secretion of multiple potentially synergistic proangiogenic growth factors. These findings suggest that autologous delivery of either native or transduced subcutaneous ASCs, which are regulated by hypoxia, may be a novel therapeutic option to enhance angiogenesis or achieve cardiovascular protection.

AB - Background-The delivery of autologous cells to increase angiogenesis is emerging as a treatment option for patients with cardiovascular disease but may be limited by the accessibility of sufficient cell numbers. The beneficial effects of delivered cells appear to be related to their pluripotency and ability to secrete growth factors. We examined nonadipocyte stromal cells from human subcutaneous fat as a novel source of therapeutic cells. Methods and Results-Adipose stromal cells (ASCs) were isolated from human subcutaneous adipose tissue and characterized by flow cytometry. ASCs secreted 1203±254 pg of vascular endothelial growth factor (VEGF) per 10 6 cells, 12 280±2944 pg of hepatocyte growth factor per 106 cells, and 1247±346 pg of transforming growth factor-β per 106 cells. When ASCs were cultured in hypoxic conditions, VEGF secretion increased 5-fold to 5980±1066 pg/10 6 cells (P=0.0016). The secretion of VEGF could also be augmented 200-fold by transfection of ASCs with a plasmid encoding VEGF (P<0.05). Conditioned media obtained from hypoxic ASCs significantly increased endothelial cell growth (P<0.001) and reduced endothelial cell apoptosis (P<0.05). Nude mice with ischemic hindlimbs demonstrated marked perfusion improvement when treated with human ASCs (P<0.05). Conclusions-Our experiments delineate the angiogenic and antiapoptotic potential of easily accessible subcutaneous adipose stromal cells by demonstrating the secretion of multiple potentially synergistic proangiogenic growth factors. These findings suggest that autologous delivery of either native or transduced subcutaneous ASCs, which are regulated by hypoxia, may be a novel therapeutic option to enhance angiogenesis or achieve cardiovascular protection.

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