Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes.
Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes.
复制标题
脂肪移植通过脂肪细胞的脱分化和再分化，诱导真皮脂肪再生，逆转皮肤纤维化。
DOI：
10.1186/s13287-022-03127-0
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发表时间：
2022-10-09
影响因子：
7.5
通讯作者：
Lu, Feng
中科院分区：
文献类型：
--
作者：
Wang, Jing;Cai, Junrong;Zhang, Qian;Wen, Jiaqing;Liao, Yunjun;Lu, Feng
局部硬皮病会导致美容毁容、关节挛缩和其他功能损害，但目前没有可用的药物可以逆转由此导致的皮肤损害。脂肪移植有利于逆转皮肤纤维化；然而，脂肪组织移植促进病变改善的机制尚未完全阐明。我们研究的目的是验证脂肪移植在逆转皮肤纤维化方面的治疗效果。来自AdipoqCreER+的腹股沟脂肪垫；他莫昔芬处理的mT/mG小鼠移植到博来霉素处理的野生型C57小鼠皮肤病变处。将Tdtomato转基因小鼠来源的脂肪细胞、脂肪来源的干细胞（ASCs）和去分化脂肪细胞（DAs）包埋在基质中，移植到博莱霉素处理的野生型C57小鼠皮肤病变下。采用transwell共培养系统验证ASCs、脂肪细胞或DAs对硬皮病成纤维细胞或单核细胞的影响。脂肪移植物的脂肪细胞可以进行去分化和再分化，使真皮脂肪组织在皮肤病变内重新积累。此外，与ASCs和脂肪细胞相比，DAs具有更强的诱导脂肪形成的能力。ASCs和DAs在诱导纤维化皮肤血管生成和抑制巨噬细胞浸润方面具有相当的作用。共培养实验显示，DAs和ASCs能够减少人硬皮病成纤维细胞中纤维化相关基因，并驱动M2巨噬细胞极化。我们的研究结果表明，脂肪细胞可以通过促进真皮脂肪组织再生、改善血管生成、抑制巨噬细胞介导的炎症和肌成纤维细胞积累，转变为功能更强的去分化状态，逆转真皮纤维化。
Localized scleroderma causes cosmetic disfigurement, joint contractures, and other functional impairment, but no currently available medications can reverse the resulting skin lesions. Fat grafting is beneficial for reversing skin fibrosis; however, the mechanism by which adipose tissue transplantation contributes to lesion improvement has not been fully clarified. The purpose of our study was to verify the therapeutic effect of fat grafts in reversing skin fibrosis. Inguinal fat pads from AdipoqCreER+;mT/mG mice, which were treated with tamoxifen, were transplanted to the skin lesion in bleomycin-treated wild-type C57 mice. Tdtomato transgenic mice-derived adipocytes, adipose-derived stem cells (ASCs), dedifferentiated adipocytes (DAs) were embedded in matrigel and transplanted beneath the skin lesion of bleomycin-treated wild-type C57 mice. A transwell co‐culture system was used to verify the effect of ASCs, adipocytes or DAs on scleroderma fibroblasts or monocytes. Adipocytes from the fat grafts could undergo dedifferentiation and redifferentiation for dermal adipose tissue re-accumulation within the skin lesion. Moreover, compared with ASCs and adipocytes, DAs show greater potency of inducing adipogenesis. ASCs and DAs showed comparable effect on inducing angiogenesis and suppressing macrophage infiltration in fibrotic skin. Co-culture assay showed that DAs and ASCs were able to reduce fibrosis-related genes in human scleroderma fibroblasts and drive M2 macrophage polarization. Our results indicated that adipocytes would transform into a more functional and dedifferentiated state and reverse dermal fibrosis, by promoting dermal adipose tissue regeneration, improving angiogenesis, suppressing macrophage-mediated inflammation and myofibroblast accumulation.
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影响因子：
4.2
作者：
PHILLIPS, RM;WASNER, CK
通讯作者：
WASNER, CK
脂肪嫁接主观改善了硬皮病患者的面部皮肤弹性和手部功能。
DOI：
10.1097/gox.0000000000003373
发表时间：
2021-01
期刊：
Plastic and reconstructive surgery. Global open
影响因子：
--
作者：
Strong AL;Adidharma W;Brown OH;Cederna PS
通讯作者：
Cederna PS
影响因子：
64.5
作者：
Festa E;Fretz J;Berry R;Schmidt B;Rodeheffer M;Horowitz M;Horsley V
通讯作者：
Horsley V
影响因子：
7.5
作者：
Manning CN;Martel C;Sakiyama-Elbert SE;Silva MJ;Shah S;Gelberman RH;Thomopoulos S
通讯作者：
Thomopoulos S
影响因子：
3.6
作者：
Kato, Harunosuke;Araki, Jun;Yoshimura, Kotaro
通讯作者：
Yoshimura, Kotaro