Augmenting mesenchymal stem cell therapy for osteoarthritis via inflammatory priming: a comparative study on mesenchymal stem cells derived from various perinatal tissue sources.
Augmenting mesenchymal stem cell therapy for osteoarthritis via inflammatory priming: a comparative study on mesenchymal stem cells derived from various perinatal tissue sources.
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DOI：
10.3389/fcell.2023.1279574
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发表时间：
2023
影响因子：
5.5
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中科院分区：
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背景：骨关节炎（OA）是一种普遍存在于老年人中的退行性疾病，由于其高发病率和致残率而面临着重大挑战。遗憾的是，对于骨性关节炎软骨的不可逆退化缺乏有效的再生治疗。间充质干细胞（MSCs）以其强大的分化和免疫调节能力而闻名，已成为OA治疗的有希望的候选者。来自围产期组织的间充质干细胞具有提取方便和伦理无争议的双重优势。然而，来自不同围产期组织来源的间充质干细胞的异质性导致了不同的治疗适应症。此外，MSCs的免疫反应可能在炎症因子的影响下被调节。方法：在这项研究中，我们从人类围产期组织的不同部位分离出间充质干细胞：脐带来源的间充质干细胞（UC-MSCs）、胎儿胎盘来源的间充质干细胞（FP-MSCs）和脐带胎盘连接来源的间充质干细胞（CPJ-MSCs）。这些细胞在体外培养，并用炎症介质白介素-1β (IL-1β)处理24小时。随后，评估MSCs在增殖、迁移和调节能力方面的变化。为了评估不同来源的间充质干细胞的抗损伤潜力，我们将原代关节软骨细胞（ACs）暴露于h2o2诱导的损伤中，并与il -1β引发的间充质干细胞共培养。研究了与OA相似的ACs的增殖、迁移和调节能力的变化。结果：IL-1β处理后，三种类型的MSCs的增殖和迁移率均下降。值得注意的是，它们的软骨分化能力有所增强。此外，不同的MSCs在体外修复受损的ACs方面表现出一定程度的功效。其中，CPJ-MSCs在促进软骨细胞增殖方面表现出较强的潜力，FP-MSCs则表现出显著的抗炎作用。结论：我们的研究结果强调了引物FP-MSCs和CPJ-MSCs减轻oa样ACs损伤的巨大能力。因此，本研究提倡在即将到来的OA治疗中使用涉及FP-MSCs和CPJ-MSCs的预处理策略。
Background: Osteoarthritis (OA), a degenerative disease prevalent among the elderly, poses significant challenges due to its high incidence and disability rates. Regrettably, there exists a lack of effective regenerative therapies for the irreversible degradation of cartilage in OA. Mesenchymal stem cells (MSCs), known for their robust differentiation and immune regulatory capabilities, have emerged as promising candidates for OA treatment. MSCs sourced from perinatal tissues offer the dual advantage of convenience in extraction and ethical non-controversy. However, the heterogeneous nature of MSCs derived from different perinatal tissue sources gives rise to varying therapeutic indications. Moreover, the immune response of MSCs may be modulated under the influence of inflammatory factors. Methods: In this study, we isolated mesenchymal stem cells from distinct parts of human perinatal tissue: umbilical cord-derived MSCs (UC-MSCs), fetal placenta-derived MSCs (FP-MSCs), and umbilical cord placental junction-derived MSCs (CPJ-MSCs). These cells were cultured in vitro and subjected to a 24-hour treatment with the inflammatory mediator Interleukin-1β (IL-1β). Subsequently, the MSCs were evaluated for changes in proliferation, migration, and regulatory capabilities. To assess the comparative anti-injury potential of MSCs from different sources, primary articular chondrocytes (ACs) were exposed to H2O2-induced injury and co-cultured with IL-1β-primed MSCs. Changes in the proliferation, migration, and regulatory abilities of ACs resembling those observed in OA were examined. Results: Following IL-1β treatment, all three types of MSCs displayed decreased rates of proliferation and migration. Notably, their chondrogenic differentiation capacities exhibited an enhancement. Additionally, diverse MSCs exhibited a degree of efficacy in restoring damaged ACs in vitro. Among these, CPJ-MSCs demonstrated superior potential in promoting cartilage cell proliferation, while FP-MSCs displayed notable anti-inflammatory effects. Conclusion: Our findings underscore the substantial capacity of primed FP-MSCs and CPJ-MSCs to alleviate the injury in OA-like ACs. Consequently, this study advocates for the prospective use of preconditioning strategies involving FP-MSCs and CPJ-MSCs in forthcoming OA therapies.