Wang Hayson Chenyu, Sun Elliot Tianyu, Zhao Robert Chunhua, Chen Bo, Han Qin, Li Na, Long Xiao, Wang Xiaojun
From the Department of Plastic Surgery.
State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital.
Plast Reconstr Surg. 2023 Jan 1;151(1):97-107. doi: 10.1097/PRS.0000000000009796. Epub 2022 Oct 7.
Although autologous fat grafting is a feasible surgical technique to improve facial deformity in patients with localized scleroderma, its success is limited by the low graft retention induced by the local inflammatory environment. This study investigated the potential effect of adipose-derived stem cells (ASCs) on skin fibrosis and fat retention in a localized scleroderma mouse model.
BALB/C nude mice that were induced by bleomycin to establish a localized scleroderma model were divided randomly into five groups: blank control; fat grafting; and low, moderate, and high doses of ASC-assisted fat grafting. The backs of the mice were subcutaneously injected with phosphate-buffered saline or fat, or fat with low, moderate, and high doses of ASCs (1 × 10 5 /mL, 5 × 10 5 /mL, and 25 × 10 5 /mL, respectively). The skin fibrosis and fat retention were analyzed after 1 month or 3 months, respectively.
Compared to the disease model group, the fat-grafting group, and the low- and moderate-dose ASC-enriched groups, the high-dose ASCs significantly attenuated skin fibrosis, inhibited the production of type III collagen and transforming growth factor-β1, increased fat graft retention, enhanced the expression of angiogenesis-related cytokines and angiogenesis, and increased the expression of adipogenesis-related cytokines.
The results demonstrated that high-dose ASCs attenuated skin fibrosis and improved fat retention in a localized scleroderma model by reducing inflammation and by promoting angiogenesis and adipogenesis. The authors further demonstrated that ASCs enhanced adipogenesis through the AKT/ERK signaling pathway.
Fat grafting has been used to treat localized scleroderma patients but with low fat retention. In this study, ASC attenuated skin fibrosis and improved fat retention in the localized scleroderma model, providing evidence for cell therapy in future application of localized scleroderma treatment.
尽管自体脂肪移植是改善局限性硬皮病患者面部畸形的一种可行手术技术，但其成功率受到局部炎症环境导致的移植脂肪留存率低的限制。本研究在局限性硬皮病小鼠模型中探究了脂肪干细胞（ASC）对皮肤纤维化和脂肪留存的潜在影响。
用博来霉素诱导建立局限性硬皮病模型的BALB/C裸鼠被随机分为五组：空白对照组；脂肪移植组；低、中、高剂量ASC辅助脂肪移植组。分别给小鼠背部皮下注射磷酸盐缓冲液、脂肪，或含低、中、高剂量ASC（分别为1×10⁵/mL、5×10⁵/mL和25×10⁵/mL）的脂肪。分别在1个月或3个月后分析皮肤纤维化和脂肪留存情况。
与疾病模型组、脂肪移植组以及低、中剂量ASC富集组相比，高剂量ASC显著减轻了皮肤纤维化，抑制了III型胶原蛋白和转化生长因子-β1的产生，增加了脂肪移植留存率，增强了血管生成相关细胞因子的表达和血管生成，并增加了脂肪生成相关细胞因子的表达。
结果表明，高剂量ASC通过减轻炎症、促进血管生成和脂肪生成，减轻了局限性硬皮病模型中的皮肤纤维化并改善了脂肪留存。作者进一步证明，ASC通过AKT/ERK信号通路增强了脂肪生成。
脂肪移植已被用于治疗局限性硬皮病患者，但脂肪留存率低。在本研究中，ASC减轻了局限性硬皮病模型中的皮肤纤维化并改善了脂肪留存，为局限性硬皮病治疗的未来细胞治疗应用提供了证据。
