Jammes Manon, Tabasi Abbas, Bach Trung, Ritter Thomas
Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland.
Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland; CURAM Centre for Research in Medical Devices, University of Galway, Galway, Ireland.
Prog Retin Eye Res. 2025 Mar;105:101325. doi: 10.1016/j.preteyeres.2024.101325. Epub 2024 Dec 20.
Affecting a large proportion of the population worldwide, corneal disorders constitute a concerning health hazard associated to compromised eyesight or blindness for most severe cases. In the last decades, mesenchymal stem/stromal cells (MSCs) demonstrated promising abilities in improving symptoms associated to corneal diseases or alleviating these affections, especially through their anti-inflammatory, immunomodulatory and pro-regenerative properties. More recently, MSC therapeutic potential was shown to be mediated by the molecules they release, and particularly by their extracellular vesicles (EVs; MSC-EVs). Consequently, using MSC-EVs emerged as a pioneering strategy to mitigate the risks related to cell therapy while providing MSC therapeutic benefits. Despite the promises given by MSC- and MSC-EV-based approaches, many improvements are considered to optimize the therapeutic significance of these therapies. This review aspires to provide a comprehensive and detailed overview of current knowledge on corneal therapies involving MSCs and MSC-EVs, the strategies currently under evaluation, and the gaps remaining to be addressed for clinical implementation. From encapsulating MSCs or their EVs into biomaterials to enhance the ocular retention time to loading MSC-EVs with therapeutic drugs, a wide range of ground-breaking strategies are currently contemplated to lead to the safest and most effective treatments. Promising research initiatives also include diverse gene therapies and the targeting of specific cell types through the modification of the EV surface, paving the way for future therapeutic innovations. As one of the most important challenges, MSC-EV large-scale production strategies are extensively investigated and offer a wide array of possibilities to meet the needs of clinical applications.
角膜疾病影响着全球很大一部分人口，对于大多数严重病例而言，它是一种与视力受损或失明相关的令人担忧的健康危害。在过去几十年中，间充质干/基质细胞（MSCs）在改善与角膜疾病相关的症状或减轻这些病症方面展现出了有前景的能力，尤其是通过其抗炎、免疫调节和促再生特性。最近，MSCs的治疗潜力被证明是由它们释放的分子介导的，特别是它们的细胞外囊泡（EVs；MSC-EVs）。因此，使用MSC-EVs成为一种开创性策略，既能降低细胞治疗相关风险，又能提供MSCs的治疗益处。尽管基于MSCs和MSC-EVs的方法带来了希望，但仍有许多改进措施被认为可以优化这些疗法的治疗意义。本综述旨在全面、详细地概述当前关于涉及MSCs和MSC-EVs的角膜治疗的知识、目前正在评估的策略以及临床应用中仍有待解决的差距。从将MSCs或其EVs封装到生物材料中以延长眼部保留时间，到用治疗药物加载MSC-EVs，目前正在考虑一系列开创性策略，以实现最安全、最有效的治疗。有前景的研究举措还包括各种基因疗法以及通过修饰EV表面靶向特定细胞类型，为未来的治疗创新铺平道路。作为最重要的挑战之一，人们正在广泛研究MSC-EVs的大规模生产策略，并提供了多种可能性来满足临床应用的需求。
