Division of Nephrology and Hypertension, Mayo Clinic, Rochester, USA.
Department of Cardiothoracic Surgery, University of Nebraska Medical Center, Omaha, USA.
Cell Transplant. 2019 Sep-Oct;28(9-10):1271-1278. doi: 10.1177/0963689719860840. Epub 2019 Jun 28.
Mesenchymal stromal/stem cells (MSCs) belong to the endogenous cellular reparative system, and can be used exogenously in cell-based therapy. MSCs release extracellular vesicles (EVs), including exosomes and microvesicles, which mediate some of their therapeutic activity through intercellular communication. We have previously demonstrated that metabolic syndrome (MetS) modifies the cargo packed within swine EV, but whether it influences their phenotypical characteristics remains unclear. This study tested the hypothesis that MetS shifts the size distribution of MSC-derived EVs. Adipose tissue-derived MSC-EV subpopulations from Lean ( = 6) and MetS ( = 6) pigs were characterized for number and size using nanoparticle-tracking analysis, flow cytometry, and transmission electron microscopy. Expression of exosomal genes was determined using next-generation RNA-sequencing (RNA-seq). The number of EV released from Lean and MetS pig MSCs was similar, yet MetS-MSCs yielded a higher proportion of small-size EVs (202.4 ± 17.7 nm vs. 280.3 ± 15.1 nm), consistent with exosomes. RNA-seq showed that their EVs were enriched with exosomal markers. Lysosomal activity remained unaltered in MetS-MSCs. Therefore, MetS alters the size distribution of MSC-derived EVs in favor of exosome release. These observations may reflect MSC injury and membrane recycling in MetS or increased expulsion of waste products, and may have important implications for development of adequate cell-based treatments.
间质/基质干细胞（MSCs）属于内源性细胞修复系统，可作为外源性细胞治疗用于临床。MSCs 释放细胞外囊泡（EVs），包括外泌体和微泡，通过细胞间通讯来发挥部分治疗作用。我们之前已经证明，代谢综合征（MetS）会改变猪 EV 中包裹的货物，但它是否会影响其表型特征尚不清楚。本研究检验了代谢综合征会改变 MSC 来源的 EV 大小分布的假设。采用纳米颗粒跟踪分析、流式细胞术和透射电子显微镜对来自 Lean（n = 6）和 MetS（n = 6）猪脂肪组织衍生的 MSC-EV 亚群进行了数量和大小的特征分析。使用下一代 RNA 测序（RNA-seq）测定了外泌体基因的表达。Lean 和 MetS 猪 MSC 释放的 EV 数量相似，但 MetS-MSCs 产生的小尺寸 EV 比例更高（202.4 ± 17.7nm 比 280.3 ± 15.1nm），与外泌体一致。RNA-seq 显示它们的 EV 富含外泌体标志物。溶酶体活性在 MetS-MSCs 中保持不变。因此，MetS 改变了 MSC 来源的 EV 大小分布，有利于外泌体的释放。这些观察结果可能反映了 MetS 中 MSC 的损伤和膜的再循环，或者是废物的排出增加，这可能对开发适当的基于细胞的治疗方法具有重要意义。
