A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn's Disease

Stem Cell Res Ther. 2024 May 14;15(1):140. doi: 10.1186/s13287-024-03746-9.

Abstract

Background: Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population.

Methods: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model.

Results: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time.

Conclusions: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing.

Trial registration: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .

Keywords: Fistula; Perianal CD; Stem cell.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase I

MeSH terms

  • Adolescent
  • Adult
  • Crohn Disease* / complications
  • Crohn Disease* / therapy
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mesenchymal Stem Cell Transplantation* / methods
  • Mesenchymal Stem Cells* / cytology
  • Middle Aged
  • Quality of Life
  • Rectal Fistula* / etiology
  • Rectal Fistula* / therapy
  • Transplantation, Homologous / methods
  • Treatment Outcome
  • Young Adult