Characterized the Adipogenic Capacity of Adipose-Derived Stem Cell, Extracellular Matrix, and Microenvironment With Fat Components Grafting.

Characterized the Adipogenic Capacity of Adipose-Derived Stem Cell, Extracellular Matrix, and Microenvironment With Fat Components Grafting.
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表征脂肪干细胞、细胞外基质和脂肪成分移植微环境的成脂能力。

DOI:
10.3389/fcell.2021.723057
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发表时间:
2021
影响因子:
5.5
通讯作者:
Zhang Y
Zhang Y
中科院分区:
生物学2区
文献类型:
--
作者:
Jiang W;Cai J;Guan J;Liao Y;Lu F;Ma J;Gao J;Zhang Y

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背景:自体脂肪移植是一种应用广泛的技术;然而,脂肪源性干细胞(ASCs)、细胞外基质(ECM)和微环境在脂肪再生中的作用尚不完全清楚。方法:获得抽脂液,通过注射器间移位去除脂肪细胞,得到无脂肪细胞脂肪(Aff)。然后将Aff暴露于致死剂量的辐射中以获得脱细胞脂肪(Df)。为了进一步去除微环境,用磷酸盐缓冲盐水(PBS)漂洗Df,得到漂洗的脱细胞脂肪(Rdf)。将绿色荧光蛋白(GFP)慢病毒(LV-GFP)转染的ASCs添加到Df中,生成细胞重组脱细胞脂肪(Crdf)。将移植物皮下移植到裸鼠体内,3个月后收获。结果:脂肪细胞(Aff)的去除不影响脂肪移植物的保留,而基质血管部分(SVF)细胞(Df)和微环境(Rdf)的额外去除导致第90天脂肪移植物的保留较差(Aff, 82±7.1%,Df, 28±6.3%,p < 0.05; Rdf, 5±1.2%,p < 0.05)。向Df (Crdf)中添加ASCs可部分恢复其再生潜能。Aff和Crdf表现出快速的血管生成和m2极化巨噬细胞浸润,而Df则表现出血管生成受损和m1极化炎症模式。GFP + ASCs参与血管生成,并在Crdf中显示内皮细胞表型。结论:脂肪ECM和微环境具有促进早期脂肪形成的能力,而单独的ECM不能在体内诱导脂肪形成。ASCs通过直接分化为内皮细胞和调节巨噬细胞极化,协调早期脂肪形成与血管生成和组织重塑,从而获得更好的长期保留和更大的组织完整性。
Background: Autologous fat grafting has been a widely used technique; however, the role of adipose-derived stem cells (ASCs), extracellular matrix (ECM), and microenvironment in fat regeneration are not fully understood. Methods: Lipoaspirates were obtained and processed by inter-syringe shifting to remove adipocytes, yielding an adipocyte-free fat (Aff). Aff was then exposed to lethal dose of radiation to obtain decellularized fat (Df). To further remove microenvironment, Df was rinsed with phosphate-buffered saline (PBS) yielding rinsed decellularized fat (Rdf). Green fluorescent protein (GFP) lentivirus (LV-GFP)-transfected ASCs were added to Df to generate cell-recombinant decellularized fat (Crdf). Grafts were transplanted subcutaneously into nude mice and harvested over 3 months. Results: Removal of adipocytes (Aff) didn’t compromise the retention of fat grafts, while additional removal of stromal vascular fraction (SVF) cells (Df) and microenvironment (Rdf) resulted in poor retention by day 90 (Aff, 82 ± 7.1% vs. Df, 28 ± 6.3%; p < 0.05; vs. Rdf, 5 ± 1.2%; p < 0.05). Addition of ASCs to Df (Crdf) partially restored its regenerative potential. Aff and Crdf exhibited rapid angiogenesis and M2-polarized macrophages infiltration, in contrast to impaired angiogenesis and M1-polarized inflammatory pattern in Df. GFP + ASCs participated in angiogenesis and displayed a phenotype of endothelial cells in Crdf. Conclusion: Adipose ECM and microenvironment have the capacity to stimulate early adipogenesis while ECM alone cannot induce adipogenesis in vivo. By directly differentiating into endothelial cells and regulating macrophage polarization, ASCs coordinate early adipogenesis with angiogenesis and tissue remodeling, leading to better long-term retention and greater tissue integrity.
DOI: 10.1038/nn.4528
发表时间: 2017-05
影响因子: 25
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