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CD34+CD146+脂肪来源基质细胞增强移植脂肪的植入。

CD34+CD146+ adipose-derived stromal cells enhance engraftment of transplanted fat.

机构信息

Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic Surgery, Stanford University School of Medicine, Stanford, California, USA.

Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.

出版信息

Stem Cells Transl Med. 2020 Nov;9(11):1389-1400. doi: 10.1002/sctm.19-0195. Epub 2020 Jun 15.

Abstract

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.

摘要

脂肪移植是一种能够重建和再生软组织的外科技术。人们认为基质血管成分中的脂肪来源基质细胞(ASCs)能够带来这些有益的效果。ASCs 被越来越多地认为是一个异质群体,由具有不同功能的多个干细胞和祖细胞亚群组成。我们假设存在具有增强的血管生成潜力的 ASC 亚群。通过流式细胞术分离 CD34+CD146+、CD34+CD146-或 CD34+未分馏(UF)的人 ASC 以比较其促血管生成因子的表达和内皮管状形成潜能。接下来,用 CD34+CD146+、CD34+CD146-、CD34+UF ASC 或不富集的脂肪抽吸物进行富集,并将其移植到免疫缺陷 CD-1 Nude 小鼠的头皮下(10000 个细胞/200μL/移植物)。在超过 8 周的时间内通过放射影像学监测脂肪保留情况,并收获脂肪移植物进行质量和血管化的组织学评估。CD34+CD146+亚群约占 ASC 的 30%,与 CD34+CD146-和 CD34+UF ASC 相比,其血管内皮生长因子和血管生成素-1的表达增加,与 CD34+CD146-ASC 相比,成纤维细胞生长因子-2的表达增加。与 CD34+CD146-ASC 相比,CD34+CD146+亚群表现出增强的管状形成诱导作用。移植后,富含 CD34+CD146+ASC 的脂肪吸收较少,组织学质量和血管化得到改善。我们已经在体外和体内鉴定出具有增强的血管生成作用的 CD34+ASC 亚群,这可能是由强有力的促血管生成因子表达增加介导的。这些发现表明,在临床环境中用 CD34+CD146+ASC 富集脂肪抽吸物可能会增强脂肪移植物的血管化和保留。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b3e/7581443/1f6d7756750a/SCT3-9-1389-g001.jpg

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