Alterations in the proangiogenic functions of adipose tissue-derived stromal cells isolated from diabetic rats
Alterations in the proangiogenic functions of adipose tissue-derived stromal cells isolated from diabetic rats
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DOI：
10.1089/scd.2008.0141
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发表时间：
2008-08-01
影响因子：
4
通讯作者：
Jung, Jin Sup
中科院分区：
文献类型：
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作者：
Kim, Hoe Kyu;Kim, Yeon Jeong;Jung, Jin Sup
糖尿病患者的心血管并发症与内皮祖细胞的促血管生成作用受损有关。在这项研究中，我们研究了脂肪组织来源的基质细胞（ASCs）在糖尿病中的功能。我们通过腹腔注射60 mg/kg链脲佐菌素（STZ）诱导大鼠I型糖尿病，并通过高脂饮食和45 mg/kg STZ联合治疗诱导大鼠II型糖尿病。从I型或II型糖尿病大鼠肩胛间和腹部脂肪组织中分离的大鼠ASCs（rASCs）的增殖能力低于对照组大鼠。在裸鼠后肢缺血模型中，糖尿病rASCs的血流恢复低于对照组大鼠。当从大鼠和人分离的ASCs暴露于高葡萄糖浓度时，与维持在对照葡萄糖浓度的ASCs相比，其在后肢缺血模型中的增殖能力和改善的血液低受到损害。然而，相同浓度的甘露醇并不影响这些特性。暴露于高浓度葡萄糖的人ASCs（hASCs）增加活性氧（ROS）的生产，和添加ROS清除剂[N-乙酰半胱氨酸（NAC）或过氧化氢酶]的高糖培养基部分降低高糖诱导的抑制作用对hASCs的增殖能力。然而，用高葡萄糖培养基处理6天的hASC在对照培养基中显示较低的增殖，这不能通过添加NAC或过氧化氢酶来恢复。这些数据表明，从糖尿病大鼠中分离并暴露于高浓度葡萄糖的ASCs具有受损的促血管生成作用，并且功能受损部分是由于长期暴露于高浓度葡萄糖产生的ROS。
Cardiovascular complications in diabetic patients have been reported to be related to the impaired proangiogenic actions of endothelial progenitor cells. In this study, we investigated the functions of adipose tissue derived stromal cells (ASCs) in diabetes. We induced type I diabetes in rats by a intraperitoneal injection of 60 mg/kg of streptozotocin (STZ) and type II diabetes by the combined treatment of high fat diet and 45 mg/kg of STZ. Rat ASCs (rASCs) isolated from the adipose tissues in the interscapular and abdominal region of type I or type II diabetic rats showed lower proliferating ability than those of control rats. Diabetic rASCs showed lower blood flow recovery than those of control rats in a hindlimb ischemia model of nude mouse. When ASCs isolated from rat and human were exposed to high glucose concentrations, their proliferating abilities and improved blood low in a hindlimb ischemia model were compromised, compared with ASCs that were maintained at control glucose concentrations. However, the same concentrations of mannitol did not affect these characteristics. Exposure of human ASCs (hASCs) to high glucose concentrations increased reactive oxygen species (ROS) production, and the addition of ROS scavengers [N-acetylcysteine (NAC) or catalase] to high glucose media partially decreased the high glucose-induced inhibitory effect on proliferating ability in hASCs. However, hASCs treated with high glucose medium for 6 days showed lower proliferation in control culture medium, which was not recovered by the addition of NAC or catalase. These data indicate that ASCs isolated from diabetic rats and exposed at high concentration of glucose have an impaired proangiogenic action and that the functional impairment is partly due to ROS generated by chronic exposure to high glucose concentrations.