Allogeneic adipose-derived stem cells promote survival of fat grafts in immunocompetent diabetic rats
Allogeneic adipose-derived stem cells promote survival of fat grafts in immunocompetent diabetic rats
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DOI：
10.1007/s00441-015-2334-1
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发表时间：
2016-05
影响因子：
3.6
通讯作者：
Jun Zhang;X. Bai;Bin Zhao;Yunchuan Wang;L. Su;Peng Chang;Xujie Wang;Shichao Han;Jianxin Gao;Xiao-long Hu;D. Hu;Xiaoyan Liu
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文献类型：
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作者：
Jun Zhang;X. Bai;Bin Zhao;Yunchuan Wang;L. Su;Peng Chang;Xujie Wang;Shichao Han;Jianxin Gao;Xiao-long Hu;D. Hu;Xiaoyan Liu
自体脂肪干细胞（ADSCs）在细胞辅助脂肪移植（CAL）中具有保护脂肪移植物的作用。然而，糖尿病改变了ADSC的内在特性，损害了它们的功能，使它们缺乏这些保护作用。我们研究来自健康供体的同种异体脂肪干细胞是否可以保护免疫活性糖尿病大鼠的脂肪移植物。同基因脂肪组织和ADSC来自糖尿病刘易斯（LEW）大鼠，而同种异体ADSC来自健康的布朗-挪威大鼠。将含有0.7ml颗粒脂肪和0.3ml 6 × 106个同种/同基因ADSCs的移植混合物注射于糖尿病LEW大鼠颅骨皮下。在第14天收获脂肪样品以评估损伤和血管形成的水平，如通过周脂蛋白A、CD 34和VEGF所示。免疫应答通过淋巴细胞毒性试验和14天时外周血中的CD 4/CD 8比率来评价。在3个月时测量脂肪移植物的体积保留。健康的同种异体ADSC在14天时增加了围脂蛋白A、CD 34和VEGF的表达水平。同种异体脂肪干细胞移植3个月后，脂肪移植物的体积保留得到改善。淋巴细胞增殖试验和免疫表型分析表明ADSCs具有低免疫原性。淋巴细胞毒性试验和CD 4/CD 8比值显示，同种异体ADSC未引起明显的免疫应答。因此，健康的同种异体脂肪干细胞可以促进脂肪移植物在这种免疫活性糖尿病大鼠模型中的存活，几乎没有或没有明显的免疫排斥反应。
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 × 106allogeneic/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.