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Clinical Applications of Mesenchymal Stem/Stromal Cell Derived Extracellular Vesicles: Therapeutic Potential of an Acellular Product

机译:间充质茎/基质细胞衍生细胞外囊泡的临床应用:无细胞产品的治疗潜力

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摘要

In the last decade, the secreting activity of mesenchymal stem/stromal cells (MSCs) has been widely investigated, due to its possible therapeutic role. In fact, MSCs release extracellular vesicles (EVs) containing relevant biomolecules such as mRNAs, microRNAs, bioactive lipids, and signaling receptors, able to restore physiological conditions where regenerative or anti-inflammatory actions are needed. An actual advantage would come from the therapeutic use of EVs with respect to MSCs, avoiding the possible immune rejection, the lung entrapment, improving the safety, and allowing the crossing of biological barriers. A number of concerns still have to be solved regarding the mechanisms determining the beneficial effect of MSC-EVs, the possible alteration of their properties as a consequence of the isolation/purification methods, and/or the best approach for a large-scale production for clinical use. Most of the preclinical studies have been successful, reporting for MSC-EVs a protecting role in acute kidney injury following ischemia reperfusion, a potent anti-inflammatory and anti-fibrotic effects by reducing disease associated inflammation and fibrosis in lung and liver, and the modulation of both innate and adaptive immune responses in graft versus host disease (GVHD) as well as autoimmune diseases. However, the translation of MSC-EVs to the clinical stage is still at the initial phase. Herein, we discuss the therapeutic potential of an acellular product such as MSC derived EVs (MSC-EVs) in acute and chronic pathologies.
机译:在过去的十年中,由于其可能的治疗作用,广泛研究了间充质茎/基质细胞(MSCs)的分泌活性。实际上,MSCS释放含有相关生物分子的细胞外囊(EVS),例如MRNA,MicroRNA,生物活性脂质和信号传导受体,能够恢复需要再生或抗炎作用的生理条件。实际优势将来自EVS关于MSC的治疗用途,避免可能的免疫排斥,肺部夹带,改善安全性,并允许越过生物屏障。对于确定MSC-EVS的有益效果的机制,仍然必须解决许多问题,因此由于隔离/纯化方法的后果,以及用于大规模生产的最佳方法临床使用。大多数临床前研究已经成功,在缺血再灌注后,在急性肾损伤中报告急性肾损伤的保护作用,通过降低肺和肝中的疾病相关的炎症和纤维化,以及调制,提高疾病相关的抗炎和抗纤维化效应。在移植物与宿主疾病(GVHD)以及自身免疫疾病中的先天和适应性免疫反应。然而,MSC-EVS对临床阶段的翻译仍处于初始阶段。在此,我们讨论了急性和慢性病变中的MSC衍生的EVS(MSC-EV)的细胞产品的治疗潜力。

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