CD34+CD146+ adipose-derived stromal cells enhance engraftment of transplanted fat.,STEM CELLS Translational Medicine

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CD34+CD146+ adipose-derived stromal cells enhance engraftment of transplanted fat.
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2020-06-15 , DOI: 10.1002/sctm.19-0195
Mimi R Borrelli ₁ , Ronak A Patel ₁ , Charles Blackshear ₁ , Stephanie Vistnes ₁ , Nestor M Diaz Deleon ₁ , Sandeep Adem ₁ , Abra H Shen ₁ , Jan Sokol ₁ , Arash Momeni ₁ , Dung Nguyen ₁ , Michael T Longaker _{1,

2} , Derrick C Wan ₁

Affiliation

Fat grafting is a surgical technique able to reconstruct and regenerate soft tissue. The adipose‐derived stromal cells (ASCs) within the stromal vascular fraction are believed to drive these beneficial effects. ASCs are increasingly recognized to be a heterogeneous group, comprised of multiple stem and progenitor subpopulations with distinct functions. We hypothesized the existence of an ASC subpopulation with enhanced angiogenic potential. Human ASCs that were CD34+CD146+, CD34+CD146−, or CD34+ unfractionated (UF) were isolated by flow cytometry for comparison of expression of proangiogenic factors and endothelial tube‐forming potential. Next, lipoaspirate was enriched with either CD34+CD146+, CD34+CD146−, CD34+ UF ASCs, or was not enriched, and grafted beneath the scalp skin of immunodeficient CD‐1 Nude mice (10 000 cells/200 μL/graft). Fat retention was monitored radiographically more than 8 weeks and fat grafts were harvested for histological assessment of quality and vascularization. The CD34+CD146+ subpopulation comprised ~30% of ASCs, and exhibited increased expression of vascular endothelial growth factor and angiopoietin‐1 compared to CD34+CD146− and CD34+ UF ASCs, and increased expression of fibroblast growth factor‐2 compared to CD34+CD146− ASCs. The CD34+CD146+ subpopulation exhibited enhanced induction of tube‐formation compared to CD34+CD146− ASCs. Upon transplantation, fat enriched CD34+CD146+ ASCs underwent less resorption and had improved histologic quality and vascularization. We have identified a subpopulation of CD34+ ASCs with enhanced angiogenic effects in vitro and in vivo, likely mediated by increased expression of potent proangiogenic factors. These findings suggest that enriching lipoaspirate with CD34+CD146+ ASCs may enhance fat graft vascularization and retention in the clinical setting.

中文翻译：

CD34+CD146+ 脂肪来源的基质细胞增强移植脂肪的植入。

脂肪移植是一种能够重建和再生软组织的外科技术。据信，基质血管部分中的脂肪来源的基质细胞 (ASC) 会产生这些有益作用。ASCs 越来越被认为是一个异质群体，由具有不同功能的多个茎和祖细胞亚群组成。我们假设存在具有增强血管生成潜力的 ASC 亚群。通过流式细胞术分离 CD34+CD146+、CD34+CD146- 或 CD34+ 未分级 (UF) 的人类 ASC，用于比较促血管生成因子的表达和内皮管形成潜力。接下来，脂肪抽吸物富含 CD34+CD146+、CD34+CD146-、CD34+ UF ASC，或者不富集，并移植到免疫缺陷 CD-1 裸鼠的头皮下（10000 个细胞/200 μL/移植物）。超过 8 周通过放射照相监测脂肪滞留并收获脂肪移植物用于质量和血管形成的组织学评估。CD34+CD146+ 亚群约占 ASC 的 30%，与 CD34+CD146- 和 CD34+ UF ASC 相比，血管内皮生长因子和血管生成素-1 的表达增加，与 CD34+CD146 相比，成纤维细胞生长因子-2 的表达增加- ASC。与 CD34+CD146-ASCs 相比，CD34+CD146+ 亚群表现出增强的管形成诱导。移植后，富含脂肪的 CD34+CD146+ASC 吸收较少，组织学质量和血管化得到改善。我们已经确定了一个 CD34+ ASCs 亚群，其在体外和体内具有增强的血管生成作用，可能是由有效的促血管生成因子的表达增加介导的。

更新日期：2020-06-15

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