<![CDATA[Stem cells, due to their unique capacities for self-renewal and differentiation, represented a highlypromising therapeutic strategy for a range of currently incurable diseases. This systematic review andmeta-analysis aimed to assess the clinical efficacy of stem cell interventions acrossneurodegenerative, cardiovascular, diabetic, and hematological disorders. A comprehensive literaturesearch of PubMed, Embase, Web of Science, and CENTRAL databases was conducted, covering theperiod from January 1995 to July 2025. A total of seventy studies were included in the qualitativesynthesis, of which forty-five studies were incorporated into the quantitative meta-analysis. Thepooled results demonstrated that stem cell therapy significantly improved functional outcomes inpatients with neurodegenerative disorders, enhanced cardiac performance in cardiovascular disease,promoted glycemic control in diabetic patients, and facilitated hematopoietic recovery inhematological conditions. Effect sizes ranged from moderate to large, indicating clinically meaningfulbenefits. Mechanistic analyses suggested that the therapeutic effects were mediated through multiplepathways, including differentiation into target cell types, paracrine signaling that modulated the localmicroenvironment, immunomodulatory actions that reduced inflammation, and stimulation ofangiogenesis that improved tissue perfusion. Despite these encouraging findings, several challengeswere identified. Heterogeneity in study protocols, including variations in stem cell type, source, dose,and delivery route, contributed to inconsistent outcomes. Potential risks such as tumorigenicity—especially with embryonic stem cells and induced pluripotent stem cells—and immune rejection wererecognized as significant safety concerns. Additionally, most studies had limited follow-up durations,restricting the evaluation of long-term efficacy and safety. Addressing these limitations throughstandardized protocols, large multicenter randomized trials, and extended follow-up was deemedessential. Collectively, the evidence supported the therapeutic potential of stem cell interventionswhile emphasizing the need for further research.]]>
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