利用牙髓干细胞的条件培养基对抗老年性黄斑变性。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research Pub Date : 2024-11-20 DOI:10.1016/j.exer.2024.110167

Giulia Carozza , Darin Zerti , Fanny Pulcini , Loreto Lancia , Simona Delle Monache , Vincenzo Mattei , Rita Maccarone

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引用次数: 0

摘要

目的：老年性黄斑变性（AMD）是导致老年人失明的主要原因。视网膜色素上皮细胞功能障碍会导致光感受器逐渐丧失，迄今为止，还没有有效的疗法来应对最严重阶段的老年黄斑变性。牙髓干细胞（DPSCs）来源容易，增殖潜力大，因此被认为有望用于再生医学。牙髓干细胞的主要优势在于其辅助免疫抑制和免疫调节能力，包括促进受损组织再生的能力。最近的研究证明了 DPSCs 条件培养基（CM）在神经退行性疾病中的治疗潜力。目的：本研究评估了 DPSCs-CM 对抗 AMD 动物模型视网膜变性的能力。在白化大鼠暴露于高强度光（LD）的前一天，经静脉注射 DPSCs-CM：结果：我们评估了视网膜功能，并按照光损伤模型的既定方案，在LD一周后进行了形态学和分子分析。低氧（HYPO-CM）或常氧（NORM-CM）条件下获得的 DPSCs-CM 能够保护视网膜功能，减少受损面积，并抵消参与视网膜变性的关键因子（如 FGF-2）的上调。此外，我们还证明，两种条件培养基都不会改变炎症激活，这表现在小胶质细胞激活和 GFAP 上调上，但体外研究表明，两种条件培养基都能显著抵消氧化应激，而氧化应激是导致老年性视网膜病变的主要原因之一：综上所述，我们的研究表明，NORM-CM 和 HYPO-CM 虽然化学成分不同，但都可以作为抵消 AMD 动物模型视网膜变性的合格候选物质。要获得最佳视网膜保护性能的条件培养基，还需要进一步的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Conditioned media from dental pulp stem cells to counteract age-related macular degeneration

查看原文本刊更多论文

Conditioned media from dental pulp stem cells to counteract age-related macular degeneration

Purpose

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. To date, there are no effective therapies to counteract AMD towards the most severe stages characterised by a progressive loss of photoreceptors triggered by retinal pigmented epithelium dysfunction. Given their easy source and their high proliferative potential, Dental Pulp Stem Cells (DPSCs) are considered promising for regenerative medicine. The main advantage of DPSCs is related to their paracrine immunosuppressive and immunoregulatory abilities, including the capability to promote regeneration of damaged tissues. Recent studies demonstrated the therapeutic potential of DPSCs-conditioned media (CM) in neurodegenerative diseases. In addition, we have already shown a differential expression of some growth factors and cytokines in CM derived from DPSCs cultured in hypoxia and normoxia conditions.

Aim

In this study we evaluated the capability of DPSCs-CM to counteract retinal degeneration in an animal model of AMD. DPSCs-CM were intravitreally injected the day before the exposure of albino rats to high intensity light (LD).

Results

We evaluated the retinal function, and we performed morphological and molecular analysis a week after the LD, in accordance with the well-established protocol of our light damage model. DPSCs-CM obtained from hypoxia (HYPO-CM) or normoxia (NORM-CM), were able to preserve the retinal function, to reduce the damaged area and to counteract the upregulation of key factors involved in retinal degeneration, like FGF-2. Furthermore, we demonstrated that neither conditioned media modified inflammatory activation, as shown by both microglia activation and GFAP upregulation, but in vitro studies demonstrated a significant effect of both CM to counteract oxidative stress, one of the main causes of AMD.

Conclusion

Taken together, our study demonstrated that NORM-CM and HYPO-CM, albeit with a different chemical composition, could represent eligible candidates to counteract retinal degeneration in an animal model of AMD. Further studies are needed to obtain conditioned media with the best performance in term of retinal protection.

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来源期刊

Experimental eye research 医学-眼科学

CiteScore

6.80

自引率

5.90%

发文量

323

审稿时长

66 days

期刊介绍： The primary goal of Experimental Eye Research is to publish original research papers on all aspects of experimental biology of the eye and ocular tissues that seek to define the mechanisms of normal function and/or disease. Studies of ocular tissues that encompass the disciplines of cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology or microbiology are most welcomed. Manuscripts that are purely clinical or in a surgical area of ophthalmology are not appropriate for submission to Experimental Eye Research and if received will be returned without review.