Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells
Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells
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DOI：
10.1161/01.cir.0000121425.42966.f1
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发表时间：
2004-03-16
期刊：
影响因子：
37.8
通讯作者：
March, KL
中科院分区：
文献类型：
--
作者：
Rehman, J;Traktuev, D;March, KL
背景-输送自体细胞以增加血管生成正在成为心血管疾病患者的一种治疗选择，但可能受到足够细胞数量可及性的限制。递送细胞的有益效果似乎与其多能性和分泌生长因子的能力有关。我们研究了nonadipose基质细胞从人皮下脂肪作为一种新的来源therapeutic cells.Methods和Results -脂肪基质细胞（ASCs）分离自人皮下脂肪组织，其特征在于通过流式细胞术。ASC每106个细胞分泌1203 +/- 254 pg的血管内皮生长因子（VEGF），每106个细胞分泌12280 +/- 2944 pg的肝细胞生长因子，每106个细胞分泌1247 +/- 346 pg的转化生长因子-β。当ASC在缺氧条件下培养时，VEGF分泌增加5倍至5980 +/- 1066 pg/10（6）个细胞（P = 0.0016）。转染VEGF基因的ASCs可使其分泌量增加200倍（P < 0.05）。缺氧ASCs条件培养液显著促进内皮细胞生长（P < 0.001），减少内皮细胞凋亡（P < 0.05）。当用人ASCs治疗时，后肢缺血的裸鼠表现出显著的灌注改善（P < 0.05）。结论-我们的实验通过证明多种潜在的协同促血管生成生长因子的分泌，描绘了容易获得的皮下脂肪基质细胞的血管生成和抗凋亡潜力。这些发现表明，自体递送受缺氧调节的天然或转导的皮下ASC可能是增强血管生成或实现心血管保护的新的治疗选择。
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-beta 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.