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诱导多能间充质干细胞与脂肪间充质干细胞来源的细胞外囊泡的比较分析:对再生医学的意义

Comparative analysis of extracellular vesicles from induced and adipose-derived Mesenchymal Stem Cells: Implications for regenerative medicine.

作者信息

Nashwan Sura, Ismail Mohammad A, Saleh Tareq, Al Hadidi Sabal, Alwohoush Enas, Sarhan Momen, Harfeil Nizar Abu, Awidi Abdalla, Ababneh Nidaa A

机构信息

Department of Applied Biology, Jordan University of Science and Technology, Irbid, Jordan.

Cell Therapy Center, The University of Jordan, Amman, Jordan.

出版信息

PLoS One. 2025 Jun 4;20(6):e0325065. doi: 10.1371/journal.pone.0325065. eCollection 2025.

Abstract

Extracellular vesicles (EVs), which include exosomes (Exos) and microvesicles (MVs), play a crucial role in intercellular communication and exert various biological activities by delivering specific cargoes of functional molecules, such as RNAs and proteins, to target cells. EVs secreted by human mesenchymal stem cells (hMSCs) have demonstrated their capacity to replace intact MSCs in tissue repair and regeneration. Induced mesenchymal stem cells (iMSCs) derived from induced pluripotent stem cells (iPSCs) present a promising alternative to traditional MSCs for producing EVs. This study aimed to establish an alternative source of EVs from iMSCs and compare them with EVs from adipose-derived MSCs (ADMSCs). Both iMSCs and ADMSCs were expanded under xeno-free culture conditions, and conditioned media were collected for EV isolation and characterization. The effects of the isolated EVs on cellular viability, apoptosis, senescence, and cell migration were evaluated. Results indicated that iMSC-EVs had a larger particle size (~1.5-fold) with no significant differences in morphology or surface markers compared to ADMSC-EVs. Furthermore, both iMSC- and ADMSC-derived EVs significantly increased HDF viability at 48 and 72 hours (p ≤ 0.01, p ≤ 0.05). Both types of EVs significantly reduced apoptosis levels (p ≤ 0.01) in both HDFs and ADMSCs, while having no effect on senescence induction (p > 0.9999). Additionally, iMSC-EVs significantly enhanced ADMSC migration (p < 0.0001), whereas the effect was less pronounced with ADMSC-EVs. iMSC-EVs present a promising and a scalable option for regenerative applications, offering advantages over ADMSC-EVs. However, further investigation is needed to fully understand their effects and underlying mechanisms.

摘要

细胞外囊泡(EVs),包括外泌体(Exos)和微囊泡(MVs),在细胞间通讯中发挥着关键作用,并通过将功能性分子(如RNA和蛋白质)的特定货物递送至靶细胞来发挥各种生物学活性。人骨髓间充质干细胞(hMSCs)分泌的EVs已证明其在组织修复和再生中替代完整MSCs的能力。源自诱导多能干细胞(iPSCs)的诱导间充质干细胞(iMSCs)为生产EVs提供了一种有前景的传统MSCs替代方案。本研究旨在建立一种来自iMSCs的EVs替代来源,并将其与来自脂肪来源的间充质干细胞(ADMSCs)的EVs进行比较。iMSCs和ADMSCs均在无血清培养条件下扩增,并收集条件培养基用于EVs的分离和表征。评估了分离的EVs对细胞活力、凋亡、衰老和细胞迁移的影响。结果表明,与ADMSC-EVs相比,iMSC-EVs具有更大的粒径(约1.5倍),在形态或表面标志物上无显著差异。此外,iMSC和ADMSC来源的EVs在48小时和72小时时均显著提高了人皮肤成纤维细胞(HDF)的活力(p≤0.01,p≤0.05)。两种类型的EVs均显著降低了HDFs和ADMSCs中的凋亡水平(p≤0.01),而对衰老诱导没有影响(p>0.9999)。此外,iMSC-EVs显著增强了ADMSC的迁移(p<0.0001),而ADMSC-EVs的作用则不太明显。iMSC-EVs为再生应用提供了一种有前景且可扩展的选择,比ADMSC-EVs具有优势。然而,需要进一步研究以充分了解它们的作用和潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e5/12136449/cc1c453b44f9/pone.0325065.g001.jpg

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