Regenerative Cell Therapeutics for Complex Perianal Fistulas: The REP-PAF Trial

Treating high anal fistulas remains a significant clinical challenge due to high recurrence rates and the risk of fecal incontinence. The newly launched REP-PAF trial in Denmark is currently investigating perianal fistula stem cell therapy as a potential solution for these difficult cases. This double-blinded, randomized controlled phase I-II trial evaluates the efficacy of adipose-derived regenerative cells (ADRCs) in patients with complex cryptoglandular perianal fistulas.

Advancing Perianal Fistula Stem Cell Therapy

The study specifically focuses on complex cryptoglandular fistulas involving more than 30% of the anal sphincter. While stem cell treatments have shown success in Crohn's-related fistulas, their application in non-Crohn's cases requires further clinical validation. Consequently, the researchers are comparing non-cultured autologous ADRCs with cultured allogeneic ADRCs. This comparison aims to determine the most effective cell source for clinical healing.

Furthermore, the surgical protocol utilizes minimal debridement combined with cell injection. This approach minimizes trauma to the anal sphincter, potentially preserving continence while promoting tissue regeneration. Additionally, the trial monitors immune responses and radiological healing through magnetic resonance imaging over 12 months. Therefore, the results could provide a robust framework for standardized regenerative treatments in proctology.

Study Objectives and Methodology

The primary outcome of the REP-PAF trial is the clinical healing rate at one year post-procedure. However, secondary outcomes remain equally critical for long-term success. These include quality of life assessments using the SF-36 survey and functional outcomes measured by the Wexner Fecal Incontinence Score. By analyzing these variables, the study provides a comprehensive view of how regenerative cells influence patient recovery. Additionally, identifying risk factors for recurrence remains a key objective for the investigators.

Frequently Asked Questions

What are ADRCs in the context of fistula repair?

ADRCs, or Adipose-Derived Regenerative Cells, are a population of cells that clinicians extract from fat tissue. They possess immunomodulatory and regenerative properties that help heal complex tissue tracts like perianal fistulas.

How is the REP-PAF study different from standard surgical treatments?

Traditional surgery often involves more extensive tissue removal or sphincter division. In contrast, this trial uses minimal surgical debridement combined with cell therapy to promote natural healing without compromising sphincter integrity.

Who is eligible for this trial?

The trial includes adults with complex cryptoglandular perianal fistulas. However, it excludes patients with active suppuration, inflammatory bowel disease, or those with a very low body mass index.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or establish a doctor-patient relationship. Always consult a qualified healthcare professional for medical concerns. Refer to the latest local and national guidelines for clinical practice.

References

Sørensen KM et al. Repairing Peri-Anal Fistulas with regenerative cell therapeutics: study protocol for a double-blinded randomized controlled phase I-II trial from Denmark (REP-PAF). Trials. 2026 Mar 04. doi: 10.1186/s13063-026-09565-y. PMID: 41782164.