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解析间充质干细胞/基质细胞衍生细胞外囊泡的异质性景观,以在转化医学中进行精确选择。

Deciphering the Heterogeneity Landscape of Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles for Precise Selection in Translational Medicine.

机构信息

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, P. R. China.

Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, P. R. China.

出版信息

Adv Healthc Mater. 2023 Jun;12(15):e2202453. doi: 10.1002/adhm.202202453. Epub 2023 Mar 26.

DOI:10.1002/adhm.202202453
PMID:36745771
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11468895/
Abstract

Mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) have been considered promising therapeutics for disease treatments. However, MSC-EVs harvested from different tissues present unique biological features reflective of their origins. The heterogeneity of MSC-EVs constitutes an important barrier to their precise application in clinical translation that may probably lead to uncertain therapeutic effects. To give hints for future clinical translation, five MSCs are employed, whose derived EVs are most intensively utilized, namely bone marrow mesenchymal stem/stromal cells (BMMSCs), umbilical cord stem/stromal cells (UCSCs), adipose-derived stem/stromal cells (ASCs), dermal stem/stromal cells (DSCs) and dental pulp stem/stromal cells (DPSCs) and the heterogeneity landscape of the corresponding MSC-EVs are documented. Overall, the basic parameters, stability, and biosafety of different MSC-EVs are indiscriminate. Strikingly, UCSC-EVs exhibit distinguishing productivity. UCSC-EVs as well as DPSC-EVs present better drug loading/delivery capacity. In addition, the heterogeneity of different MSC-EVs in cargo diversity, cellular affinity, organ biodistribution, and therapeutic effects may cue the rational selection in different disease treatments. Through a combined assessment, a rational strategy is combined for selecting MSC-EVs in future clinics. Offering a panoramic view of MSC-EVs harvested from different tissues, the current study may provide guidelines for the precise selection of MSC-EVs in next-generation therapeutics.

摘要

间充质干细胞/基质细胞衍生的细胞外囊泡(MSC-EVs)被认为是疾病治疗有前途的治疗方法。然而,从不同组织中收获的 MSC-EVs 具有反映其起源的独特生物学特征。MSC-EVs 的异质性是其在临床转化中精确应用的一个重要障碍,这可能导致治疗效果不确定。为了为未来的临床转化提供线索,使用了五种最常用于衍生 EV 的 MSC,即骨髓间充质干细胞(BMMSCs)、脐带干细胞/基质细胞(UCSCs)、脂肪来源的干细胞/基质细胞(ASCs)、真皮干细胞/基质细胞(DSCs)和牙髓干细胞/基质细胞(DPSCs),并记录了相应 MSC-EVs 的异质性景观。总体而言,不同 MSC-EVs 的基本参数、稳定性和生物安全性是不分轩轾的。引人注目的是,UCSC-EVs 表现出区分生产力。UCSC-EVs 和 DPSC-EVs 具有更好的药物加载/输送能力。此外,不同 MSC-EVs 在货物多样性、细胞亲和力、器官生物分布和治疗效果方面的异质性可能提示在不同疾病治疗中进行合理选择。通过综合评估,为未来的临床实践制定了选择 MSC-EVs 的合理策略。通过对不同组织中收获的 MSC-EVs 的全面评估,本研究可为下一代治疗中精确选择 MSC-EVs 提供指导。

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