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Background: Crohn's disease is a chronic, relapsing form of inflammatory bowel disease marked by severe gastrointestinal inflammation and a broad range of debilitating symptoms. Despite advances in medical treatments, achieving sustained remission remains challenging for many patients. This umbrella review aims to consolidate evidence from various systematic reviews to evaluate the efficacy and safety of stem cell therapies in treating Crohn's disease., Methods: This review followed the Joanna Briggs Institute methodology and adhered to PRISMA guidelines. A literature search of PubMed, Web of Science, Embase, and the Cochrane Library covered records up to 20 April 2024. Only systematic reviews and meta-analyses on stem cell therapy for Crohn's disease were considered. Data were extracted and analyzed for clinical efficacy indicators like remission induction and safety metrics, including adverse events and mortality rates., Results: Sixteen systematic reviews were included, spanning studies conducted between 2009 and 2023. Stem cell therapy showed a pooled risk ratio (RR) of 1.299 (95% CI: 1.192-1.420) for clinical remission, indicating a 29.9% increased likelihood of remission compared to controls. The pooled RR for healing perianal Crohn's disease was 1.358 (95% CI: 1.13-1.631), suggesting a 35.8% increased likelihood of healing. A pooled RR of 1.481 (95% CI: 1.036-2.116) shows a 48.1% higher immediate fistula closure rate with stem cell therapy. For long-term outcomes, a RR of 1.422 (95% CI: 1.091-1.854) indicates a 42.2% increased likelihood of maintaining closure. However, stem cell therapy did not significantly impact Crohn's Disease Activity Index (CDAI) (RR: 1.154, 95% CI: 0.193-6.883) and Perianal Disease Activity Index (PDAI) scores (mean difference at 12 weeks: -0.505, 95% CI: -2.481 to 1.471; mean difference at 24 weeks: -0.338, 95% CI: -1.638 to 0.963). The safety profile was comparable to conventional therapies, with a pooled RR of 0.972 (95% CI: 0.739-1.278) for adverse events and 1.136 (95% CI: 0.821-1.572) for serious adverse events., Conclusion: Stem cell therapy offers significant progress in treating Crohn's disease, particularly in complex cases, by improving fistula closure rates and suggesting potential as a supplementary therapy. Its safety profile aligns with conventional treatments, yet ongoing clinical trials are crucial to optimize its use. Continual research will enable healthcare providers to tailor more effective treatment strategies for this challenging condition., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)