Sept. 16, 2017
Perianal fistulas occur in up to 20 percent of patients with Crohn's disease (CD). This disease complication recurs frequently, causes significant morbidity and profoundly impacts patients' quality of life. To address this challenge, Mayo Clinic researchers conducted a six-month phase I trial (Stem Cells on Matrix Plugs) to evaluate whether application of concentrated mesenchymal stem cells (MSCs) contained in a bioabsorbable matrix (MSC-matrix) can heal a fistula. This research, published in Gastroenterology, has yielded some encouraging preliminary results.
Mayo researchers recruited 12 adult patients, ages 18 to 65, with a single draining fistula for at least three months, without proctitis, who did not respond to anti-tumor necrosis factor therapy. MSCs were extracted from adipose tissue, cryopreserved, then thawed and returned to culture with a fistula matrix and allowed to multiply until the matrix was impregnated with a mean dose of 20 million stem cells. Six weeks after the MSC harvest, a Mayo surgeon then placed the matrix intraoperatively in study subjects.
The primary endpoint of this trial was to determine the safety and feasibility of the treatment. The study's secondary endpoint of efficacy was defined by clinical and radiographic markers.
Complete response was defined by complete cessation of drainage, both spontaneously and upon gentle compression during physical exam conducted at six months after matrix placement. Criteria for a partial clinical response included a decrease in drainage and symptoms, as reported by the patient.
- Nine of the 12 patients had complete clinical healing within three months after treatment, and 10 of 12 patients (83.3 percent) had complete clinical healing at six months. Of the two patients who did not achieve clinical healing, one developed an abscess at three months that required seton placement, and the other experienced persistent drainage.
- Eleven patients underwent no change in their primary CD therapy throughout the six-month study. One patient chose to switch medical therapy (from infliximab to adalimumab).
- Four patients received antibiotics (< 30-day course) at the discretion of the clinical management team.
Criteria for radiographic response included decreases in the diameter and length of the T2-weighted hyperintense fistula tract on T2-weighted fast spin-echo images (expressed as percent change from baseline), without development of abscess or additional problems with the treated fistula, and without increase in the Van Assche magnetic resonance imaging perianal fistula severity score.
- Radiographic criteria for response were demonstrated in 10 of 12 patients (83 percent).
- Mean absolute changes in length and diameter of fistula tract were decreases of 23.5 millimeter (mm) and 5.0 mm, respectively, in patients who responded to the treatment; and increases of 0.2 mm and 10 mm, respectively, in patients who did not respond to treatment.
- A significant decrease occurred in the length of T2-weighted hyperintensity within the fistula (median decrease, 22 percent; range, -5 to 100 percent; p = 0.01); and a nonsignificant decrease in diameter occurred (median decrease, 57 percent; range, -36 to 100 percent; p = 0.307), with negative values representing an increase in fistula size in the treatment failures.
- Van Assche perianal severity scores decreased (from a median of 13 to a median of 9; p = 0.0008), without worsening in any patients.
"We are pleased with these initial results," says William A. Faubion, M.D., a gastroenterologist at Mayo Clinic's campus in Rochester, Minnesota, who served as senior author of the Gastroenterology article and study sponsor. "Our data collectively demonstrate that MSC-MATRIX shows promise as new treatment for fistulizing perianal Crohn's disease."
Dr. Faubion notes that plans for a larger study are currently underway, which the research team hopes will yield additional evidence about this treatment's feasibility, safety and efficacy.
For more information
Dietz AB, et al. Autologous mesenchymal stem cells, applied in a bioabsorbable matrix, for treatment of perianal fistulas in patients with Q1 Crohn's disease. Gastroenterology. 2017;153:59.