Aging and diabetes impair the neovascular potential of adipose-derived stromal cells.
Aging and diabetes impair the neovascular potential of adipose-derived stromal cells.
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DOI：
10.1097/prs.0b013e3181954d08
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发表时间：
2009-02
影响因子：
3.6
通讯作者：
Gurtner GC
中科院分区：
文献类型：
--
作者：
El-Ftesi S;Chang EI;Longaker MT;Gurtner GC
衰老和糖尿病是伤口愈合不良和组织再生的主要危险因素，反映了对缺血性损伤的反应能力受损。作者探讨了脂肪来源的基质细胞在老年和1型和2型糖尿病患者中固有的新生血管潜能。从年轻、年老、链脲佐菌素诱导和db/db糖尿病小鼠中分离脂肪来源的基质细胞，在体外暴露于常氧和缺氧环境中。测量血管内皮生长因子（VEGF）的表达、增殖和小管化。评估从脂肪来源的基质细胞培养中获得的条件培养基刺激人脐静脉内皮细胞增殖的能力（n = 3和n = 3）。在常氧和低氧条件下，年轻脂肪来源的基质细胞的VEGF生成、增殖和小管形成水平明显高于年老、链脲佐菌素诱导和db/db小鼠。尽管老年和糖尿病脂肪来源的间质细胞在缺氧条件下保留了上调VEGF分泌、增殖和小管形成的能力，但与年轻对照组相比，这种反应减弱了。与衰老、链脲佐菌素诱导和db/db脂肪来源的基质细胞相比，这些细胞在体外常氧培养条件培养基中获得的条件培养基也具有显著提高人脐静脉内皮细胞增殖的能力。这种效应在从低氧脂肪来源的基质细胞培养中获得的条件培养基中被放大。该研究表明，衰老和1型和2型糖尿病损害了脂肪源性间质细胞的内在功能；然而，这些细胞可能仍然是血管生成细胞的合适来源，可以潜在地改善缺血组织的新生血管。
Aging and diabetes are major risk factors for poor wound healing and tissue regeneration that reflect an impaired ability to respond to ischemic insults. The authors explored the intrinsic neovascular potential of adipose-derived stromal cells in the setting of advanced age and in type 1 and type 2 diabetes. Adipose-derived stromal cells isolated from young, aged, streptozotocin-induced, and db/db diabetic mice were exposed to normoxia and hypoxia in vitro. Vascular endothelial growth factor (VEGF) expression, proliferation, and tubulization were measured. Conditioned media harvested from adipose-derived stromal cell cultures were assessed for their ability to stimulate human umbilical vein endothelial cell proliferation (n = 3 and n = 3). Young adipose-derived stromal cells demonstrated significantly higher levels of VEGF production, proliferation, and tubulogenesis than those derived from aged, streptozotocin-induced, and db/db mice in both normoxia and hypoxia. Although aged and diabetic adipose-derived stromal cells retained the ability to up-regulate VEGF secretion, proliferation, and tubulogenesis in response to hypoxia, the response was blunted compared with young controls. Conditioned media derived from these cells cultured in normoxia in vitro also had a significantly greater ability to increase human umbilical vein endothelial cell proliferation compared with media harvested from aged, streptozotocin-induced, and db/db adipose-derived stromal cells. This effect was magnified in conditioned media harvested from hypoxic adipose-derived stromal cell cultures. This study demonstrates that aging and type 1 and type 2 diabetes impair intrinsic adipose-derived stromal cell function; however, these cells may still be a suitable source of angiogenic cells that can potentially improve neovascularization of ischemic tissues.