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Mesenchymal stem cell based therapies for uveitis: a systematic review of preclinical studies

Eye (2024)Cite this article

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Abstract

Cell therapy has shown promising results for treating uveitis in preclinical studies. As the field continues to grow towards clinical translation, it is important to review and critically appraise existing studies. Herein, we analysed and critically appraised all preclinical studies using cell therapy or cell derived extracellular vesicles (EVs) for uveitis, and provided insight into mechanisms regulating ocular inflammation. We used PubMed, Medline, and Embase to search for preclinical studies examining stem cell therapy (e.g., mesenchymal stem cells [MSC]) and secreted EVs. All included studies were assessed for quality using the SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) checklist. Sixteen preclinical studies from 2011 to 2022 were analysed and included in this review of which 75% (n = 12) focused only on cell therapy, 18.7% (n = 3) studies focused on EVs, and 6.3% (n = 1) study focused on both cells and EVs. MSCs were the most common type of cells used in preclinical studies (n = 15) and EVs were commonly isolated from MSCs (n = 3). Overall, both MSCs and EVs showed improvements in ocular inflammation (seen on fundoscopy/slit lamp and histology) and electroretinogram outcomes. Overall, MSC and MSC-derived EVs shown great potential as therapeutic agents for treating uveitis. Unfortunately, small sample size, risk of selection/performance bias, and lack of standardized cell harvesting or delivery protocols are some factors which limits clinical translation. Large scaled, randomized preclinical studies are required to understand the full potential of MSCs for treating uveitis.

摘要

细胞疗法在治疗葡萄膜炎的临床前研究中展示出良好的结果。随着这一领域不断向临床转化, 对现有研究进行回顾性和批判性地评估非常重要。在此, 我们分析并严格评估了使用细胞疗法或细胞产生的胞外囊泡 (EVs) 进行葡萄膜炎研究的临床前研究, 并深入探讨了调节眼部炎症的机制。我们使用PubMed、Medline和Embase检索了有关干细胞疗法 (如间充质干细胞 [MSC]) 和分泌的EVs的临床前研究。我们使用实验动物实验系统审查中心 (SYRCLE) 核对表对所有纳入的研究进行了质量评估。

本综述分析并纳入了2011年至2022年的16项临床前研究, 其中75% (n = 12) 研究只关注了细胞疗法, 18.7% (n = 3) 的研究关注了EVs, 而6.3% (n = 1) 的研究同时关注了细胞和EVs。间充质干细胞 (MSC) 是在临床前研究中使用最多的细胞类型 (n = 15), EVs通常从MSC中分离出来 (n = 3) 。总之, MSC和EVs对眼部炎症 (通过眼底镜/裂隙灯和组织学观察) 和视网膜电图结果均有改善。

总之, MSC和MSC衍生的EVs作为治疗葡萄膜炎的药物显示出了巨大的潜力。遗憾的是, 样本量小, 存在选择/选择偏倚的风险, 以及缺乏标准化的细胞采集或输送方案等因素限制了临床转化。需要进行大规模的、随机的临床前研究, 以了解MSC治疗葡萄膜炎的全部潜力。

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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Author information

Author notes

  1. These authors contributed equally: Pushpinder Kanda, Arnav Gupta.

Authors and Affiliations

  1. Eye Institute, University of Ottawa, Ottawa, ON, Canada

    Pushpinder Kanda, Jobanpreet Dhillon, Deeksha Kundapur & Chloe C. Gottlieb

  2. Department of Medicine, University of Calgary, Calgary, AB, Canada

    Arnav Gupta

  3. College of Public Health, Kent State University, Kent, OH, USA

    Arnav Gupta

  4. Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON, Canada

    Chloe C. Gottlieb

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Contributions

PK was responsible for conception of study. PK, AG were responsible for designing the study protocol, screening studies, data acquisition, analysis, organizing tables/figures and drafting the manuscript. JD, DK were involved in data analysis, organizing tables/figures, and writing the manuscript. CG and PK was involved in helping revise the protocol, and editing manuscript. Final version of the manuscript was approved by all authors.

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Correspondence to Pushpinder Kanda.

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Kanda, P., Gupta, A., Dhillon, J. et al. Mesenchymal stem cell based therapies for uveitis: a systematic review of preclinical studies. Eye (2024). https://doi.org/10.1038/s41433-024-03057-6

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