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Allogeneic adipose-derived stem cells promote survival of fat grafts in immunocompetent diabetic rats

机译:异源脂肪干细胞在免疫能力强的糖尿病大鼠中促进脂肪移植物的存活

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Autologous adipose-derived stem cells (ADSCs) can protect fat grafts in cell-assisted lipotransfer (CAL). However, diabetes alters the intrinsic properties of ADSCs and impairs their function so that they lack these protective effects. We investigate whether allogeneic ADSCs from healthy donors could protect fat grafts in immunocompetent diabetic rats. Syngeniec adipose tissues and ADSCs were derived from diabetic Lewis (LEW) rats, whereas allogeneic ADSCs were from healthy brown-Norway rats. A grafted mixture containing 0.7 ml granule fat and 0.3 ml 6 x 10(6) allogeneic/syngeneic ADSCs was injected subcutaneously on the skulls of diabetic LEW rats. Fat samples were harvested to evaluate the levels of injury and vascularization as shown by perilipin A, CD34 and VEGF at 14 days. The immune response was evaluated with a lymphocytotoxicity test and the CD4/CD8 ratio in peripheral blood at 14 days. The volume retention of fat grafts was measured at 3 months. Healthy allogeneic ADSCs increased the expression levels of perilipin A, CD34 and VEGF at 14 days. The volume retention of fat grafts was improved by allogeneic ADSCs at 3 months. ADSCs were demonstrated to have low immunogenicity by the lymphocyte proliferation test and immunophenotype including MHC and co-stimulatory markers. The lymphocytotoxicity test and CD4/CD8 ratio indicated no obvious immune response elicited by allogeneic ADSCs. Thus, healthy allogeneic ADSCs can promote the survival of fat grafts in this immunocompetent diabetic rat model, with little or no obvious immune rejection.
机译:自体脂肪干细胞(ADSC)可以在细胞辅助脂质转移(CAL)中保护脂肪移植物。但是,糖尿病会改变ADSC的内在特性并损害其功能,因此它们缺乏这些保护作用。我们调查了来自健康供体的同种异体ADSC是否可以保护具有免疫能力的糖尿病大鼠的脂肪移植物。同源脂肪组织和ADSCs来自糖尿病的Lewis(LEW)大鼠,而同种异体ADSCs来自健康的棕色-挪威大鼠。将包含0.7 ml颗粒脂肪和0.3 ml 6 x 10(6)同种/同基因ADSC的移植混合物皮下注射到糖尿病LEW大鼠的头骨上。收获脂肪样品以评估损伤和血管形成的水平,如在第14天的脂蛋白A,CD34和VEGF所示。在14天时,通过淋巴细胞毒性试验和外周血CD4 / CD8比评估免疫应答。在3个月时测量脂肪移植物的体积保留率。健康的同种异体ADSCs在14天时增加了periplipin A,CD34和VEGF的表达水平。异体ADSCs在3个月时改善了脂肪移植物的体积保留。淋巴细胞增殖试验和包括MHC和共刺激标记物在内的免疫表型证明ADSC具有低免疫原性。淋巴细胞毒性试验和CD4 / CD8比值表明,同种异体ADSCs没有引起明显的免疫反应。因此,在这种具有免疫能力的糖尿病大鼠模型中,健康的同种异体ADSC可以促进脂肪移植物的存活,几乎没有免疫排斥或没有明显的免疫排斥。

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