Comparison Study of Stem Cell-Derived Extracellular Vesicles for Enhanced Osteogenic Differentiation

Comparison Study of Stem Cell-Derived Extracellular Vesicles for Enhanced Osteogenic Differentiation
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DOI:
10.1089/ten.tea.2020.0194
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发表时间:
2020-11-19
影响因子:
4.1
通讯作者:
Lee, Sang Jin
Lee, Sang Jin
中科院分区:
医学3区
文献类型:
--
作者:
Pishavar, Elham;Copus, Joshua S.;Lee, Sang Jin

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影响陈述骨组织工程方法旨在通过提供支架材料、细胞和生物活性因子的组合来增强骨再生,从而克服当前与自体骨移植相关的挑战。最近显示,来自骨髓间充质干细胞(BMSC)的细胞外囊泡(EV)可以增强成骨分化并改善骨矿物质沉积。在此,源自胎盘干细胞(PSC)的EV具有相当的提高成骨能力的能力。 PSC 具有较高的增殖能力、无需侵入性操作即可收获以及产生大量 EV 等优点。使用这些EV的可行性在临床转化研究中尤其重要,因为临床转化研究需要大量的EV才能实现这种效果。干细胞来源的细胞外囊泡(EV)在再生医学和组织工程领域显示出巨大的前景。最近,人类骨髓间充质干细胞(BMSC)衍生的EV已被考虑用于骨组织工程应用。在这项研究中,我们评估了胎盘干细胞 (PSC) 衍生的 EV 的成骨能力,并将其与充分表征的 BMSC 衍生的 EV 进行比较。在成骨分化后的三个指定时间点(0、7和21天)提取EV。结果表明,PSC 衍生的 EV 比 BMSC 衍生的 EV 具有更高的蛋白质和脂质浓度。提取的 EV 通过观察其形态和大小分布进行表征,然后利用新一代测序确定其 microRNA (miRNA) 图谱。 EV 中总共鉴定出 306 个 miRNA,其中 64 个在 PSC 衍生的 EV 中显着表达,与成骨分化相关。体外成骨分化研究表明,与早期衍生的 EV 相比,晚期(提取 21 天)衍生的 EV 具有更高的成骨增强能力。我们证明,源自 PSC 的 EV 可以成为骨组织工程应用的 EV 的新来源。
Impact statementBone tissue engineering approaches aim to overcome current challenges associated with autologous bone grafts by delivering a combination of scaffolding material, cells, and bioactive factors to enhance bone regeneration. Extracellular vesicles (EVs) from bone marrow-derived mesenchymal stem cells (BMSCs) have recently been shown to enhance osteogenic differentiation and improve bone mineral deposition. Herein, EVs derived from placental stem cells (PSCs) have a comparative ability to improve osteogenic capability. PSCs have advantages such as higher proliferation capacity, the ability to be harvested without an invasive procedure, and they produce larger amounts of EVs. The feasibility of using these EVs will be especially important in clinical translational studies, which require substantial amounts of EVs to achieve this effect.Stem cell-derived extracellular vesicles (EVs) have shown great promise in the field of regenerative medicine and tissue engineering. Recently, human bone marrow-derived mesenchymal stem cell (BMSC)-derived EVs have been considered for bone tissue engineering applications. In this study, we evaluated the osteogenic capability of placental stem cell (PSC)-derived EVs and compared them to the well-characterized BMSC-derived EVs. EVs were extracted from three designated time points (0, 7, and 21 days) after osteogenic differentiation. The results showed that the PSC-derived EVs had much higher protein and lipid concentrations than EVs derived from BMSCs. The extracted EVs were characterized by observing their morphology and size distribution before utilizing next-generation sequencing to determine their microRNA (miRNA) profiles. A total of 306 miRNAs within the EVs were identified, of which 64 were significantly expressed in PSC-derived EVs that related to osteogenic differentiation. In vitro osteogenic differentiation study indicated the late-stage (21-day extracted)-derived EVs higher osteogenic enhancing capability when compared with the early stage-derived EVs. We demonstrated that EVs derived from PSCs could be a new source of EVs for bone tissue engineering applications.