Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, The Netherlands (S.I.V.D.W., F.M.M., J.P.G.S., P.V.) and CDL Research, University Medical Center Utrecht, The Netherlands (P.V.).
Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, The Netherlands (S.I.V.D.W., F.M.M., J.P.G.S., P.V.) and CDL Research, University Medical Center Utrecht, The Netherlands (P.V.)
Pharmacol Rev. 2023 Sep;75(5):1043-1061. doi: 10.1124/pharmrev.123.000841. Epub 2023 Jun 6.
Extracellular vesicles (EVs) are cell-derived membrane-enclosed particles that are involved in physiologic and pathologic processes. EVs are increasingly being studied for therapeutic applications in the field of regenerative medicine. Therapeutic application of stem cell-derived EVs has shown great potential to stimulate tissue repair. However, the exact mechanisms through which they induce this effect have not been fully clarified. This may to a large extent be attributed to a lack of knowledge on EV heterogeneity. Recent studies suggest that EVs represent a heterogeneous population of vesicles with distinct functions. The heterogeneity of EVs can be attributed to differences in their biogenesis, and as such, they can be classified into distinct populations that can then be further subcategorized into various subpopulations. A better understanding of EV heterogeneity is crucial for elucidating their mechanisms of action in tissue regeneration. This review provides an overview of the latest insights on EV heterogeneity related to tissue repair, including the different characteristics that contribute to such heterogeneity and the functional differences among EV subtypes. It also sheds light on the challenges that hinder clinical translation of EVs. Additionally, innovative EV isolation techniques for studying EV heterogeneity are discussed. Improved knowledge of active EV subtypes would promote the development of tailored EV therapies and aid researchers in the translation of EV-based therapeutics to the clinic. SIGNIFICANCE STATEMENT: Within this review we discuss the differences in regenerative properties of extracellular vesicle (EV) subpopulations and implications of EV heterogeneity for development of EV-based therapeutics. We aim to provide new insights into which aspects are leading to heterogeneity in EV preparations and stress the importance of EV heterogeneity studies for clinical applications.
细胞外囊泡 (EVs) 是一种细胞来源的膜封闭颗粒，参与生理和病理过程。EVs 在再生医学领域的治疗应用中越来越受到关注。干细胞衍生的 EVs 的治疗应用显示出刺激组织修复的巨大潜力。然而，它们诱导这种效应的确切机制尚未完全阐明。这在很大程度上可能归因于对 EV 异质性的了解不足。最近的研究表明，EVs 代表具有不同功能的囊泡的异质群体。EVs 的异质性可以归因于它们的生物发生的差异，因此，可以将它们分类为不同的群体，然后进一步细分为各种亚群。更好地了解 EV 异质性对于阐明它们在组织再生中的作用机制至关重要。本综述提供了有关与组织修复相关的 EV 异质性的最新见解，包括导致这种异质性的不同特征以及 EV 亚型之间的功能差异。它还揭示了阻碍 EV 临床转化的挑战。此外，还讨论了用于研究 EV 异质性的创新 EV 分离技术。对活性 EV 亚型的更好了解将促进针对特定 EV 治疗的开发，并帮助研究人员将基于 EV 的治疗方法转化为临床应用。
在本综述中，我们讨论了细胞外囊泡 (EV) 亚群的再生特性差异以及 EV 异质性对 EV 治疗开发的影响。我们旨在提供新的见解，了解哪些方面导致了 EV 制剂的异质性，并强调 EV 异质性研究对临床应用的重要性。
