A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in...

Area of Science:

• Gastroenterology
• Regenerative Medicine
• Immunology

Background:

• Perianal fistulas (PF) impact one-third of Crohn's disease (CD) patients, with limited treatment alternatives.
• Research on the safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) for PF in CD patients is scarce.

Purpose of the Study:

• To evaluate the safety and efficacy of allogeneic BMSCs in treating refractory perianal fistulizing Crohn's disease.
• To assess clinical severity, biomarkers, and radiological changes over 104 weeks.

Main Methods:

• An open-label, phase I/II, single-arm study involving local administration of allogeneic BMSCs.
• Patients with refractory perianal fistulas received BMSCs; assessments included clinical evaluation, biomarkers, and MRI.
• Safety and efficacy were primary and secondary objectives, respectively, with remission defined by fistula closure and response by drainage reduction.

Main Results:

• Ten patients (80% male, mean age 27.4 years) were enrolled. Three experienced self-resolving adverse events; none were persistent.
• At 24 weeks, 20% achieved remission and 70% showed response. These rates were maintained through 104 weeks.
• Significant improvements were observed in perianal disease activity index (P=.008), Van Assche Index (P=.008), and quality-of-life (P=.001) over time.

Conclusions:

• Allogeneic BMSCs represent a safe and effective therapeutic option for perianal fistulizing Crohn's disease.
• Treatment with BMSCs leads to significant improvements in both clinical symptoms and radiological healing.
• Further research is warranted to explore the long-term efficacy and potential of BMSCs in managing complex fistulizing CD.