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

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.