Fibrin glue with mesenchymal stem cells for perianal fistulas: a systematic review and meta-analysis

Objectives: perianal fistulas (PFs) are often refractory to standard management. Cell therapy strategies using mesenchymal stem cells (MSCs) carried in fibrin glue (FG) have shown promising results in regenerative medicine. Thus, the objective of our study was to assess the efficacy and safety of local FG combined with MSCs for PFs. Methods: electronic databases were searched for studies that reported efficacy and/or safety of local FG combined with MSCs therapy for PFs. The PRISMA guideline was followed. We performed a meta-analysis using the meta package in R and Rev-Man software. Results: after screening, a total of ten studies were identified. The overall clinical healing rate (HR) of PFs after local FG combined with MSCs therapy was 63 % (95 % confidence interval [CI]: 0.52, 0.73). Magnetic resonance imaging (MRI) served as the primary modality for assessing fistula healing outcomes, and the pooled HR was 51 % (95 % CI: 0.38, 0.64). Fistula healing was defined as the complete reepithelialization of external openings, and the pooled HR was 70 % (95 % CI: 0.62, 0.78). Furthermore, our meta-analysis revealed that the pooled HR for PFs in the context of Crohn's disease (CD) was elevated compared to PFs not associated with CD (63 % vs 59 %, respectively). Compared with local FG-alone therapy, local FG combined with MSCs therapy resulted in a higher HR of PFs (odds ratio [OR] = 3.18; 95 % CI: 1.80,5.61; p < 0.0001). No major MSCs-related adverse event has been reported. Conclusion: our study indicated that local FG therapy combined with MSCs treatment for PFs is a promising strategy and that it achieves a higher HR for PFs compared to local FG-alone therapy. This therapy strategy also appears to offer superior treatment for PFs associated with CD. Future assessment in randomized controlled studies is warranted.