Orally derived mesenchymal stem cells in the treatment of vascular diseases: a systematic review and meta-analysis

Orally derived mesenchymal stem cells (OMSCs) are an emerging source of cells for treating vascular diseases (VDs). In this systematic review and meta-analysis, for the first time, we reviewed the published preclinical studies that examined the potential of OMSCs and their secretome in treating VDs, focusing on their efficacy and therapeutic mechanism. We electronically searched PubMed, Embase, and Web of Science, from the inception of the databases to December 31, 2024, for relevant literature from peer-reviewed journals. The studies focused on treating VDs in animal models using the OMSC-based strategy were included in the review. The articles were classified by disease, injury model, and outcome. A meta-analysis of the OMSC treatment effects on the cerebral ischemia (CI) infarct volume was conducted using random-effects and fixed-effects models. Forty-one studies were included and classified by type: CI, hypoxic-ischemic encephalopathy (HIE), myocardial ischemia (MI), hindlimb ischemia (HI), and others. Each study presented varying degrees of evidence that OMSCs had positive biological and functional effects on the treatment outcomes of VDs, mainly via paracrine effects. Pooled analysis showed that the effect of OMSC treatment compared with control on infarct volume was − 2.19 (95% confidence interval: − 3.01, − 1.37, p < 0.01) with the random-effects model and − 1.87 (95% confidence interval: − 2.44, − 1.29, p < 0.01) with the fixed-effects model. These results showed that OMSCs can significantly reduce the infarct volume in animal models of CI. Overall, OMSCs show promising potential for treating VDs mainly because of their secretome. However, before moving on to clinical trials, more high-quality preclinical studies with detailed analyses of possible off-target effects are needed.