Feng Hao, Qiu Lihong, Zhang Teng, Yu Houyou, Ma Xianjie, Su Yingjun, Zheng Hui, Wang Yong, Yi Chenggang
From the *Department of Dermatology, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan; †Department of Plastic Surgery, ‡Department of Emergency, Xijing Hospital; and §Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
Ann Plast Surg. 2017 Apr;78(4):460-466. doi: 10.1097/SAP.0000000000000968.
Autologous fat grafting is a prevalent technique used for soft-tissue augmentation; however, the poor survival rate of the grafted tissue remains a drawback of this method. Although adipose-derived stem cells (ASCs) are an attractive candidate for enhancing graft retention, the poor posttransplantation viability of these cells limits their application. Here we investigated whether overexpression of the antiapoptotic protein heat-shock protein 70 (Hsp70) could enhance ASCs' therapeutic potential for fat transplant survival.
Recombinant adenoviral vectors were used to overexpress Hsp70 in ASCs isolated from a healthy woman. The Hsp70 expression was assessed by quantitative real-time polymerase chain reaction and Western blot analyses. The adipose tissue granules aspirated from another woman were mixed with ASCs expressing green fluorescent protein (GFP)-tagged Hsp70 (group A) or GFP alone (group B), untreated ASCs (group C), and phosphate-buffered saline (group D). Fat mixtures were then injected subcutaneously into the backs of nude mice, and graft survival was compared after 3 months.
Adipose-derived stem cells transduced with recombinant adenoviral vectors exhibited significantly increased Hsp70 expression in vitro. Meanwhile, weight retention analyses demonstrated that fat grafts using the group A cell population exhibited significantly higher survival rates than the other treatment groups in vivo. Moreover, histological analyses revealed that fat grafts containing GFP-Hsp70-expressing ASCs yielded significantly lower levels of tissue fibrosis and fat cysts/vacuoles, higher capillary densities, and increased numbers of viable adipocytes than the control groups.
Our data indicate that Hsp70 overexpression enhances the efficacy of ASC therapy by improving the survival and quality of the transplanted fat tissues.
自体脂肪移植是一种用于软组织填充的常用技术；然而，移植组织存活率低仍是该方法的一个缺点。尽管脂肪来源干细胞（ASC）是提高移植脂肪留存率的一个有吸引力的选择，但这些细胞移植后的低存活率限制了它们的应用。在此，我们研究了抗凋亡蛋白热休克蛋白70（Hsp70）的过表达是否能增强ASC对脂肪移植存活的治疗潜力。
使用重组腺病毒载体在从一名健康女性分离出的ASC中过表达Hsp70。通过定量实时聚合酶链反应和蛋白质印迹分析评估Hsp70的表达。将从另一名女性吸出的脂肪组织颗粒与表达绿色荧光蛋白（GFP）标记的Hsp70的ASC（A组）或仅表达GFP的ASC（B组）、未处理的ASC（C组）以及磷酸盐缓冲盐水（D组）混合。然后将脂肪混合物皮下注射到裸鼠背部，3个月后比较移植脂肪的存活率。
用重组腺病毒载体转导的脂肪来源干细胞在体外表现出Hsp70表达显著增加。同时，重量留存分析表明，在体内，使用A组细胞群体的脂肪移植存活率显著高于其他治疗组。此外，组织学分析显示，与对照组相比，含有表达GFP - Hsp70的ASC的脂肪移植组织纤维化和脂肪囊肿/空泡水平显著降低、毛细血管密度更高且存活脂肪细胞数量增加。
我们的数据表明，Hsp70过表达通过提高移植脂肪组织的存活率和质量来增强ASC治疗的效果。
