Diabetes impairs adipose tissue-derived stem cell function and efficiency in promoting wound healing
Diabetes impairs adipose tissue-derived stem cell function and efficiency in promoting wound healing
复制标题
DOI：
10.1111/wrr.12051
复制
发表时间：
2013-07-01
影响因子：
2.9
通讯作者：
Odorisio, Teresa
中科院分区：
文献类型：
--
作者：
Cianfarani, Francesca;Toietta, Gabriele;Odorisio, Teresa
脂肪组织源干细胞(ASCs)在组织修复治疗中的应用日益受到重视。最近的证据表明，在创伤愈合受损的动物模型中，ASCs促进了皮肤修复。为了评估自体ASCs与同种异体ASCs在治疗糖尿病溃疡中的治疗活性，我们对糖尿病ASCs的功能进行了表征，并与非糖尿病ASCs相比，研究了它们促进伤口愈合的潜力。对链脲佐菌素诱导的1型糖尿病小鼠的脂肪组织来源的细胞进行了分析，要么是新鲜分离的基质血管分数(SVF)，要么是经过一次传代培养(ASCs)。糖尿病ASCs的增殖能力和迁移能力降低。在糖尿病SVF和培养的ASCs中，表面标志物的表达发生了变化，干细胞标志物阳性细胞减少。糖尿病小鼠的ASCs释放较少的肝细胞生长因子、血管内皮生长因子-A和胰岛素样生长因子-1，这些生长因子在皮肤修复中起重要作用。因此，糖尿病ASCs的培养上清液对角质形成细胞和成纤维细胞的增殖和迁移的促进能力降低。与从非糖尿病小鼠分离的细胞相比，糖尿病小鼠伤口上应用糖尿病SVF的治疗潜力被钝化。我们的数据表明，糖尿病改变了ASC的固有特性，损害了它们的功能，从而影响了自体治疗糖尿病溃疡的治疗潜力。
Adipose tissue-derived stem cells (ASCs) are gaining increasing consideration in tissue repair therapeutic application. Recent evidence indicates that ASCs enhance skin repair in animal models of impaired wound healing. To assess the therapeutic activity of autologous vs. allogeneic ASCs in the treatment of diabetic ulcers, we functionally characterized diabetic ASCs and investigated their potential to promote wound healing with respect to nondiabetic ones. Adipose tissue-derived cells from streptozotocin-induced type 1 diabetic mice were analyzed either freshly isolated as stromal vascular fraction (SVF), or following a single passage of culture (ASCs). Diabetic ASCs showed decreased proliferative potential and migration. Expression of surface markers was altered in diabetic SVF and cultured ASCs, with a reduction in stem cell marker-positive cells. ASCs from diabetic mice released lower amounts of hepatocyte growth factor, vascular endothelial growth factor (VEGF)-A, and insulin-like growth factor-1, growth factors playing important roles in skin repair. Accordingly, the supernatant of diabetic ASCs manifested reduced capability to promote keratinocyte and fibroblast proliferation and migration. Therapeutic potential of diabetic SVF administered to wounds of diabetic mice was blunted as compared with cells isolated from nondiabetic mice. Our data indicate that diabetes alters ASC intrinsic properties and impairs their function, thus affecting therapeutic potential in the autologous treatment for diabetic ulcers.