Department of Pediatric Surgery, University of Texas McGovern Medical School, Houston, Texas, USA.
McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Stem Cells. 2018 Jan;36(1):79-90. doi: 10.1002/stem.2730. Epub 2017 Nov 16.
Extracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSCs) have been proposed to be a key mechanistic link in the therapeutic efficacy of cells in response to cellular injuries through paracrine effects. We hypothesize that inflammatory stimulation of MSCs results in the release of EVs that have greater anti-inflammatory effects. The present study evaluates the immunomodulatory abilities of EVs derived from inflammation-stimulated and naive MSCs (MSCEv and MSCEv, respectively) isolated using a current Good Manufacturing Practice-compliant tangential flow filtration system. Detailed characterization of both EVs revealed differences in protein composition, cytokine profiles, and RNA content, despite similarities in size and expression of common surface markers. MSCEv further attenuated release of pro-inflammatory cytokines in vitro when compared to MSCEv, with a distinctly different pattern of EV-uptake by activated primary leukocyte subpopulations. The efficacy of EVs was partially attributed to COX2/PGE expression. The present study demonstrates that inflammatory stimulation of MSCs renders release of EVs that have enhanced anti-inflammatory properties partially due to COX2/PGE pathway alteration. Stem Cells 2018;36:79-90.
细胞外囊泡（EVs）由间充质基质细胞（MSCs）分泌，被认为是细胞通过旁分泌作用对细胞损伤产生治疗效果的关键机制联系。我们假设 MSCs 的炎症刺激导致释放具有更大抗炎作用的 EVs。本研究使用符合现行良好生产规范的切向流过滤系统评估了来自炎症刺激和未刺激的 MSCs（分别为 MSCEv 和 MSCEv）衍生的 EV 的免疫调节能力。尽管在大小和常见表面标志物的表达上存在相似性，但对两种 EV 的详细特征分析显示其蛋白组成、细胞因子谱和 RNA 含量存在差异。与 MSCEv 相比，MSCEv 进一步减弱了体外促炎细胞因子的释放，同时通过激活的原始白细胞亚群摄取 EV 的模式明显不同。EV 的功效部分归因于 COX2/PGE 的表达。本研究表明，MSCs 的炎症刺激导致释放具有增强抗炎特性的 EV，部分原因是 COX2/PGE 途径的改变。干细胞 2018;36:79-90。
