Introduction
Perianal fistulas represent a major therapeutic challenge in Crohn’s disease, affecting up to 40% of patients and significantly impairing quality of life. Despite the advent of biologic therapies, failure rates remain high, necessitating the exploration of innovative strategies. Mesenchymal stem cells (MSCs), owing to their immunomodulatory, anti-inflammatory, and regenerative properties, have emerged as a promising therapeutic alternative.
Aims & Methods
We conducted a prospective, single-center, open-label, single-blind randomized study, enrolling 34 adult patients with Crohn’s disease complicated by complex perianal fistulas refractory to conventional therapies. All patients underwent a single local injection of autologous bone marrow-derived MSCs. Clinical, biological, and radiological assessments (pelvic MRI) were performed at 6, 12, and 24 weeks post-injection. The primary endpoints were complete clinical closure of external fistulous openings (EFOs) and radiological regression of fistulous tracts. Secondary endpoints included changes in Crohn’s Disease Activity Index (CDAI), C-reactive protein (CRP) levels, and quality of life assessed by a simplified IBDQ-9 score.
Results
- At 6 weeks: 32.3% (11/34) of patients achieved complete closure of EFOs, and 47.0% showed significant reduction in fistula drainage.
- At 12 weeks: 52.9% (18/34) achieved complete closure, and 23.5% (8/34) exhibited partial healing (>50% closure).
- At 24 weeks: 64.7% (22/34) had durable complete closure, while 20.6% (7/34) maintained partial healing.
Pelvic MRI evaluation revealed:
- A reduction in the number of active fistulous tracts in 73.5% of patients by week 12.
- Complete disappearance of fistulous tracts in 58.8% of cases by week 24.
Biological outcomes:
- CRP levels decreased from 13.8 ± 7.2 mg/L at baseline to 6.2 ± 3.4 mg/L at 6 weeks, 4.7 ± 2.5 mg/L at 12 weeks, and 3.9 ± 2.1 mg/L at 24 weeks (p < 0.001).
- CDAI scores improved from 176.2 ± 48.7 at baseline to 143.7 ± 41.2 at 6 weeks, 127.1 ± 37.5 at 12 weeks, and 122.4 ± 35.1 at 24 weeks (p < 0.001).
- Quality of life (IBDQ-9 score) improved by an average of 34% over 24 weeks (p < 0.001).
Safety:
- No serious adverse events or systemic infections were reported.
Mild transient local pain at the injection site occurred in 8.8% of patients (3/34).
Conclusion
Our study demonstrates that autologous bone marrow-derived MSC therapy is a safe, effective, and innovative option for the management of complex perianal fistulas in Crohn’s disease. With an overall clinical response rate of 85.3% at 24 weeks, and significant improvements in inflammatory markers, fistula morphology, and quality of life, this cellular therapy emerges as a leading alternative in the therapeutic arsenal. Larger, multicenter, randomized controlled trials are warranted to validate these findings and refine optimal indications and protocols.
References
- Panés J, García-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in Crohn’s disease: results from the ADMIRE-CD trial extension. Lancet Gastroenterol Hepatol. 2021;6(11):889-97.
- Lightner AL, Raffals LE, Mathis KL, Dozois EJ, Pemberton JH, Cima RR. Stem cell therapy for treatment of perianal Crohn’s disease: a systematic review and meta-analysis. Dis Colon Rectum. 2022;65(4):539-49.
- Zhou Q, Zhou J, Qi X, Xu L, Yang H, Xie W, et al. Long-term outcomes of autologous adipose-derived stem cells in complex perianal fistulas in Crohn’s disease. Stem Cells Transl Med. 2023;12(2):210-20.
