Supplementation with Extracellular Vesicles Derived from Adipose-Derived Stem Cells Increases Fat Graft Survival and Browning in Mice: A Cell-Free Approach to Construct Beige Fat from White Fat Grafting.
Supplementation with Extracellular Vesicles Derived from Adipose-Derived Stem Cells Increases Fat Graft Survival and Browning in Mice: A Cell-Free Approach to Construct Beige Fat from White Fat Grafting.
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补充脂肪干细胞衍生的细胞外囊泡可增加小鼠脂肪移植物的存活率和褐变：一种从白色脂肪移植物构建米色脂肪的无细胞方法。
DOI：
10.1097/prs.0000000000006740
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发表时间：
2020
影响因子：
3.6
通讯作者：
Yi Yang-Yan
中科院分区：
文献类型：
--
作者：
Zhu Yuan-Zheng;Zhang Jing;Hu Xuan;Wang Zhao-Hui;Wu Shu;Yi Yang-Yan
背景：越来越多的证据表明，脂肪干细胞衍生的细胞外囊泡可增强脂肪移植物的存活率和白色脂肪组织的褐变。我们评估补充脂肪干细胞来源的细胞外囊泡是否促进脂肪移植物的存活和褐变。方法：将脂肪干细胞来源的细胞外囊泡每周一次注射到 C57BL/6 小鼠的脂肪移植物中，直至移植后第 12 周。在移植后第 2、4 和 12 周后收集移植物并称重。 评估移植物的形态、新生血管形成和M2巨噬细胞的比例。检测细胞外囊泡促进巨噬细胞极化和儿茶酚胺分泌的能力。还验证了棕色脂肪分化的诱导是细胞外囊泡还是细胞外囊泡极化的M2巨噬细胞的旁分泌作用。结果：来自脂肪干细胞的细胞外囊泡处理的移植物表现出米色脂肪再生增强，新生血管形成、M2巨噬细胞比例和去甲肾上腺素分泌增加。 移植后第 4 周。移植后第 12 周观察到保留增加，纤维化和坏死减少。巨噬细胞摄取细胞外囊泡促进 M2 型极化和儿茶酚胺分泌，同时抑制 M1 型极化。值得注意的是，能量消耗增加的褐变脂肪分化只能通过来自细胞外囊泡极化 M2 巨噬细胞的条件培养基来促进，而不能通过细胞外囊泡本身来促进。结论：补充来自脂肪干细胞的细胞外囊泡可增加脂肪移植物的存活和褐变，通过细胞外囊泡极化 M2 巨噬细胞的分泌 儿茶酚胺促进米色脂肪再生。
Background:Growing evidence has demonstrated that adipose-derived stem cell-derived extracellular vesicles enhance the survival of fat grafts and the browning of white adipose tissue. We evaluated whether supplementation with adipose-derived stem cell-derived extracellular vesicles promotes the survival and browning of fat grafts.Methods:Extracellular vesicles derived from adipose-derived stem cells were injected into fat grafts of C57BL/6 mice once per week until postgraft week 12. The grafts were collected and weighed after postgraft weeks 2, 4, and 12. The histological morphology, neovascularization, and the proportion of M2 macrophages of grafts were evaluated. The ability of extracellular vesicles to promote macrophage polarization and catecholamine secretion was detected. Whether the inducement of browning adipose differentiation is extracellular vesicles or the paracrine effect of M2 macrophages polarized by extracellular vesicles was also verified.Results:Grafts treated by extracellular vesicles derived from adipose-derived stem cells showed enhanced beige adipose regeneration with increased neovascularization, M2 macrophage proportion, and norepinephrine secretion at postgraft week 4. Increased retention and decreased fibrosis and necrosis were noted at postgraft week 12. The extracellular vesicles uptake by macrophages promoted M2 type polarization and catecholamine secretion while suppressing M1 type polarization. Of note, browning adipose differentiation with enhanced energy expenditure could be promoted only by the conditioned medium from extracellular vesicle–polarized M2 macrophages but not by extracellular vesicles themselves.Conclusions:Supplementation with extracellular vesicles derived from adipose-derived stem cells increases fat graft survival and browning by which extracellular vesicles–polarized M2 macrophages secrete catecholamines to promote beige adipose regeneration.