Introduction

Perianal fistulas, which may be difficult to treat, are a common complication of Crohn's disease, which is a chronic disorder that is complex and difficult to control. The purpose of our research was to determine whether or not it would be possible and safe to inject hematopoietic mesenchymal stem cells into these patients' bodies, as well as to investigate the effectiveness of the therapy over a period of forty-eight weeks.

Aims & Methods

Between April 2022 and November 2023, we went through the process of conducting a prospective observational research at our hospital. Twenty-three adult patients who were diagnosed with Crohn's disease and perianal fistulas were included in our study. Hematopoietic stem cells were extracted from the bone marrow of every individual patient and delivered at a dosage of 3x10^6 cells. The first half of the cells were injected into the entrance of the internal fistula, while the second half was put into the opening of the exterior fistula. The surgery was followed by the administration of an intravenous stem cell infusion to a certain number of individuals.

Results

36 percent of patients had achieved full closure of all external fistula openings by the 12th week of therapy, and this percentage improved to 52 percent by the 48th week of treatment. The majority of patients who originally presented with more than two external openings showed considerable improvement when at least one of the holes was closed.
It is important to highlight that throughout the follow-up period, one patient had an anal abscess that required further draining, while all other patients did not develop any abscesses. Furthermore, the level of luminal disease activity, as determined by CDAI, remained low throughout the duration of the follow-up period.

Conclusion

In conclusion, the findings of our research indicate that the use of hematopoietic stem cell injections for the treatment of perianal fistulas in patients with Crohn's disease is not only possible but also risk-free. According to the clinical findings, which are consistent with those published in reference studies, the closure rate at one year is fifty percent. In addition, this therapy has been linked to an improvement in patients' perineal activity levels as well as their quality of life.

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.

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

1. 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.
2. 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.
3. 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.