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

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

Abstract

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.