Mesenchymal stem cells transplantation for perianal fistulas: a systematic review and meta-analysis of clinical trials

Abstract

Background Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative impact on quality of life and a tremendous burden to the healthcare system. Treatment of anal fistulas usually consists of anal surgery; however, results of closure rates are not satisfactory especially with complex perianal fistulas, after which many patients may suffer from anal incontinence. Recently, the administration of mesenchymal stem cells (MSCs) has shown promising efficacy. Herein, we aim to explore whether MSCs are effective for complex perianal fistulas and if they have either short-term, medium-term, long-term or over-long-term efficacy. Additionally, we want to elucidate whether factors such as drug dosage, MSC source, cell type, and disease aetiology influence treatment efficacy. Main body of the abstract We searched four online databases and analysed data based on information within the clinical trials registry. The outcomes of eligible trials were analysed with Review Manager 5.4.1. Relative risk and related 95% confidence interval were calculated to compare the effect between the MSCs and control groups. In addition, the Cochrane risk of bias tool was applied to evaluate the bias risk of eligible studies. Meta-analyses showed that therapy with MSCs was superior to conventional treatment for complex perianal fistulas in short-, long- and over-long-term follow-up phases. However, there was no statistical difference in treatment efficacy in the medium term between the two methods. Subgroup meta-analyses showed factors including cell type, cell source and cell dosage were superior compared to the control, but there was no significant difference between different experimental groups of those factors. Besides, local MSCs therapy has shown more promising results for fistulas as a result of Crohn’s Disease (CD). Although we tend to maintain that MSCs therapy is effective for cryptoglandular fistulas equally, more studies are needed to confirm this conclusion in the future. Short conclusion MSCs Transplantation could be a new therapeutic method for complex perianal fistulas of both cryptoglandular and CD origin showing high efficacy in the short-term to over-long-term phases, as well as high efficacy in sustained healing. The difference in cell types, cell sources and cell dosages did not influence MSCs’ efficacy.

Ovine Forestomach Matrix Implant for Surgical Management in Perianal Fistulas: A Retrospective Case-Series

“…Interestingly, OFM has shown the ability to recruit mesenchymal stem cells (MSCs) [24] and retain growth factors (KGF, BMP, PDGF, VEGF) and chemokines that promote tissue growth [21]. Using the same principle, the use of stem cell therapy is an increasingly common treatment strategy for PFs [14] with demonstrated instances of success, particularly in PFs associated with Crohn's disease [32]. We hypothesize that OFM may be acting as not only a classic anal stula plug but may additionally be acting as a multimodal therapy due to recruitment of progenitor cells.…”

“…Similarly, ablative techniques have demonstrated success in mitigating sphincter damage but carry a high recurrence rate with moderate clinical e cacy [12,13]. Stem cell therapies have also shown value, particularly with respect to stulas related to Crohn's disease, but future studies evaluating PFs of other etiologies are needed [14,15]. Therefore, a need still exists for a minimally invasive, clinically effective, simple, and cost-effective alternative to traditional surgical interventions for PF.…”

Stem Cells and Stem Cell-Derived Factors for the Treatment of Inflammatory Bowel Disease with a Particular Focus on Perianal Fistulizing Disease: A Minireview on Future Perspectives

“…These promising results generated a wave of phase 1, phase 2, and phase 3 trials to study the safety and efficacy of using MSCs to treat perianal CD (Table 1 ). Despite the heterogeneity in protocols using allogeneic or autologous MSCs, derived from both bone marrow or adipose tissue, administered at various doses, delivered as a singular or repeat injection, and delivered with or without scaffolding, the results of all completed trials have been very encouraging with regard to both safety and efficacy [ 42 , 49 ]. Safety has focused on the rate of perianal abscess formation and perianal pain to determine whether injection of MSCs increases either.…”

Comments on: “Mesenchymal stem cells transplantation for perianal fistulas: a systematic review and meta-analysis of clinical trials”

“…I read with great interest the meta-analysis by Wang et al [ 1 ] reporting the mesenchymal stem cells (MSCs) transplantation for perianal fistulas (PFs). I appreciate the authors’ hard work.…”