on March 1, 2004
Circulation. 2004
Published online before print March 1, 2004, doi: 10.1161/01.CIR.0000121425.42966.F1
Published online before print March 1, 2004, doi: 10.1161/01.CIR.0000121425.42966.F1
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© American Heart Association, Inc.
Basic Science Reports |
Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells
From the Krannert Institute of Cardiology (J.R., D.T., J.L., S.M.-C., B.H.J., K.L.M.), Division of Nephrology (C.J.T.-G.), Division of Endocrinology (J.E.B., R.V.C.), Indiana Center for Vascular Biology and Medicine (J.R., D.T., J.L., S.M.-C., C.J.T.-G., J.E.B., C.L.P., B.H.J., R.V.C., K.L.M.), Indiana University School of Medicine and the R.L. Roudebush VA Medical Center (K.L.M.), Indianapolis, Ind.
Correspondence to Keith L. March, MD, PhD, Indiana Center for Vascular Biology & Medicine, 975 W Walnut St IB 441, Indianapolis, IN 46202. E-mail kmarch{at}iupui.edu
Received November 7, 2003; de novo received December 17, 2003; revision received January 26, 2004; accepted January 28, 2004.
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 106 cells, 12 280±2944 pg of hepatocyte growth factor per 106 cells, and 1247±346 pg of transforming growth factor-ß per 106 cells. When ASCs were cultured in hypoxic conditions, VEGF secretion increased 5-fold to 5980±1066 pg/106 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.
Key Words: endothelium • angiogenesis • cells
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