成体干细胞来源的线粒体转移联合姜黄素对年龄相关性黄斑变性模型中ARPE-19细胞的治疗潜力

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2024-12-18 DOI:10.1016/j.tice.2024.102687

Kamil Can Kılıç , Gökhan Duruksu , Ahmet Öztürk , Selenay Furat Rençber , Buket Kılıç , Yusufhan Yazır

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引用次数: 0

摘要

目的：利用视网膜模型评估姜黄素、hWJ-MSCs-mt或hE-MSCs-mt对老年性黄斑变性（AMD）的影响，探讨来自人类沃顿氏果冻来源的间充质干细胞（hWJ-MSCs-mt）和人子宫内膜来源的间充质干细胞（hE-MSCs-mt）的线粒体转移以及姜黄素作为线粒体效率低下引起的黄斑变性（AMD）的潜在治疗方法。方法：用ARPE-19细胞建立AMD体外模型。将细胞暴露于0-50 μM姜黄素中24 小时，通过评估其活力来确定最佳浓度。在最佳过氧化氢（H2O2）浓度下，免疫荧光检测SOD1、TNF-α和TGF-β水平。β-半乳糖苷酶染色和DCFH分析评价h2o2诱导的细胞衰老。免疫荧光检测REP65、CRALBP1 （RLBP1）、Pink1和Parkin的表达，而qRT-PCR检测与姜黄素和hWJ-MSCs-mt或hE-MSCs-mt联合处理后Nrf2、Ire1a、ARMS2、HTRA1、RPE65、RLBP1、NOX4和TOMM20的表达。结果：姜黄素通过调节SOD1、TNF-α、TGF-β、DCFH和MDA水平，改善h2o2诱导氧化应激下ARPE-19细胞的存活。hWJ-MSCs-mt的转移增加了RLBP1和Parkin的表达，而姜黄素则降低了Parkin的表达。he - msc -mt的转移上调了Parkin、RPE65、Pink1和RLBP1的表达，姜黄素增强了RPE65的表达。hWJ-MSCs-mt与姜黄素联合更有效地下调应激相关基因Nrf2、Ire1α、NOX4的表达，提高线粒体功能基因TOMM20的表达。姜黄素- he - msc -mt转移可协同增强AMD模型中视网膜健康标志物（RPE65、RLBP1）的表达，并下调损伤相关基因（HTRA1、ARMS2）的表达。结论：姜黄素联合hWJ-MSCs-mt或hE-MSCs-mt具有抗炎作用，是治疗黄斑变性的潜在药物；然而，需要进一步的体内和人体研究来证实其有效性和安全性。

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Therapeutic potential of adult stem cells-derived mitochondria transfer combined with curcumin administration into ARPE-19 cells in age-related macular degeneration model

Objective

Mitochondria transfer from human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs-mt) and human endometrium-derived mesenchymal stem cells (hE-MSCs-mt), along with curcumin, were explored as potential treatments for age-related macular degeneration (AMD) caused by mitochondrial inefficiency, using a retinal model to assess impacts of curcumin and hWJ-MSCs-mt or hE-MSCs-mt on AMD.

Methods

ARPE-19 cells established an in vitro AMD model. Cells were exposed to 0–50 μM curcumin for 24 hours to determine optimal concentration by assessing their viability. Immunofluorescence examined SOD1, TNF-α, and TGF-β levels at optimal hydrogen peroxide (H₂O₂) concentration. β-galactosidase staining and DCFH analysis evaluated H₂O₂-induced cellular senescence. Immunofluorescence assessed REP65, CRALBP1 (RLBP1), Pink1, and Parkin expression, whereas qRT-PCR analyzed Nrf2, Ire1a, ARMS2, HTRA1, RPE65, RLBP1, NOX4, and TOMM20 expression following co-treatment with curcumin and hWJ-MSCs-mt or hE-MSCs-mt.

Results

Curcumin improved ARPE-19 cell survival under H₂O₂-induced oxidative stress by regulating SOD1, TNF-α, TGF-β, DCFH, and MDA levels. hWJ-MSCs-mt transfer increased RLBP1 and Parkin expression, whereas curcumin reduced Parkin expression. hE-MSCs-mt transfer upregulated Parkin, RPE65, Pink1, and RLBP1 expressions, with curcumin enhancing RPE65 expression. hWJ-MSCs-mt and curcumin combined more effectively downregulated expressions of stress-related genes (Nrf2, Ire1α, NOX4) and improved expression of mitochondrial function gene (TOMM20). hE-MSCs-mt transfer with curcumin synergistically enhanced expression of retinal health markers (RPE65, RLBP1) and downregulated expression of damage-associated genes (HTRA1, ARMS2) in AMD models.

Conclusion

Curcumin combined with hWJ-MSCs-mt or hE-MSCs-mt is a potential AMD therapy owing to its anti-inflammatory properties; however, further in vivo and human studies are needed to confirm its efficacy and safety.

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.