The antifibrotic adipose-derived stromal cell: Grafted fat enriched with CD74+ adipose-derived stromal cells reduces chronic radiation-induced skin fibrosis.,STEM CELLS Translational Medicine

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The antifibrotic adipose-derived stromal cell: Grafted fat enriched with CD74+ adipose-derived stromal cells reduces chronic radiation-induced skin fibrosis.
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2020-06-20 , DOI: 10.1002/sctm.19-0317
Mimi R Borrelli ₁ , Ronak A Patel ₁ , Sandeep Adem ₁ , Nestor M Diaz Deleon ₁ , Abra H Shen ₁ , Jan Sokol ₁ , Sara Yen ₁ , Erin Y Chang ₂ , Rahim Nazerali ₁ , Dung Nguyen ₁ , Arash Momeni ₁ , Kevin C Wang ₂ , Michael T Longaker _{1,

3} , Derrick C Wan ₁

Affiliation

Fat grafting can reduce radiation‐induced fibrosis. Improved outcomes are found when fat grafts are enriched with adipose‐derived stromal cells (ASCs), implicating ASCs as key drivers of soft tissue regeneration. We have identified a subpopulation of ASCs positive for CD74 with enhanced antifibrotic effects. Compared to CD74− and unsorted (US) ASCs, CD74+ ASCs have increased expression of hepatocyte growth factor, fibroblast growth factor 2, and transforming growth factor β3 (TGF‐β3) and decreased levels of TGF‐β1. Dermal fibroblasts incubated with conditioned media from CD74+ ASCs produced less collagen upon stimulation, compared to fibroblasts incubated with media from CD74− or US ASCs. Upon transplantation, fat grafts enriched with CD74+ ASCs reduced the stiffness, dermal thickness, and collagen content of overlying skin, and decreased the relative proportions of more fibrotic dermal fibroblasts. Improvements in several extracellular matrix components were also appreciated on immunofluorescent staining. Together these findings indicate CD74+ ASCs have antifibrotic qualities and may play an important role in future strategies to address fibrotic remodeling following radiation‐induced fibrosis.

中文翻译：

抗纤维化脂肪来源的基质细胞：富含 CD74+ 脂肪来源的基质细胞的移植脂肪可减少慢性辐射引起的皮肤纤维化。

脂肪移植可以减少辐射引起的纤维化。当脂肪移植物富含脂肪来源的基质细胞 (ASC) 时，结果会得到改善，这表明 ASC 是软组织再生的关键驱动因素。我们已经确定了一个 CD74 阳性的 ASC 亚群，具有增强的抗纤维化作用。与 CD74- 和未分类 (US) ASCs 相比，CD74+ ASCs 增加了肝细胞生长因子、成纤维细胞生长因子 2 和转化生长因子 β3 (TGF-β3) 的表达，并降低了 TGF-β1 的水平。与用来自 CD74- 或美国 ASC 的培养基培养的成纤维细胞相比，用来自 CD74+ ASC 的条件培养基培养的真皮成纤维细胞在刺激时产生较少的胶原蛋白。移植后，富含 CD74+ ASC 的脂肪移植物降低了上覆皮肤的硬度、真皮厚度和胶原蛋白含量，并降低更多纤维化真皮成纤维细胞的相对比例。免疫荧光染色也对几种细胞外基质成分的改进表示赞赏。这些发现共同表明 CD74+ ASCs 具有抗纤维化特性，可能在未来解决辐射诱导纤维化后纤维化重塑的策略中发挥重要作用。

更新日期：2020-06-20

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