Abstract
BACKGROUND: Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that often leads to the development of complex perianal fistulas, significantly impairing patients' quality of life. Conventional medical and surgical treatments offer limited long-term efficacy, with high recurrence rates and associated complications. Adipose-derived stem cell therapy (ADSCT) has emerged as a promising regenerative therapy due to its anti-inflammatory and tissue-regenerative properties. However, discrepancies in clinical outcomes across studies warrant a systematic evaluation of its efficacy and safety. OBJECTIVE: This systematic review aims to critically assess the efficacy, safety, and recurrence rates of ADSCT for complex perianal fistulas in Crohn's disease patients, summarizing data from randomized controlled trials and observational studies. METHODS: This review included 19 studies published between 2009 and 2024 involving Crohn's disease patients treated with either autologous or allogeneic ADSCT. Extracted data included patient demographics, fistula characteristics, treatment protocols, and clinical outcomes such as fistula closure, partial healing, time to healing, recurrence, and adverse events. Study selection followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and is illustrated in a PRISMA flow diagram. Risk of bias was assessed using the Cochrane Risk of Bias Tool for randomized controlled trials and adapted versions of the Newcastle-Ottawa Scale (NOS) and MINORS criteria for observational studies. Studies were categorized as excellent, good, or fair based on their total quality score. RESULTS: Fistula closure rates ranged from 23.1 % to 91 %, with an overall average of 62.5 %. Partial healing rates varied widely, between 9 % and 93.3 %. Time to healing ranged from 8 to 48 weeks, with an average of 25.3 weeks. Recurrence rates were reported in over half of the studies and reached up to 38.5 %, with a mean recurrence rate of 19.2 %. The majority of adverse events were mild and transient, including local inflammation, discomfort, and minor infections. No serious (Grade 3 or 4) complications were reported. Risk of bias assessment classified one study as excellent, two as good, and two as fair in methodological quality. CONCLUSION: Adipose-derived stem cell therapy demonstrates promising efficacy and a favorable safety profile for the treatment of complex perianal fistulas in Crohn's disease. While ADSCT may achieve meaningful clinical response and symptom relief in a substantial proportion of patients, variability in outcomes and study designs highlights the need for standardized protocols and long-term follow-up in future trials.