November 13, 2015
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Mesenchymal stem cells promote healing of perianal fistulas in Crohn's patients

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Locally administered allogeneic bone marrow-derived mesenchymal stromal cells appeared to promote healing of perianal fistulas in patients with Crohn’s disease in a recent study.

“[Despite] the wide range of available therapies nowadays, durable remission rate of complex perianal fistulizing Crohn’s disease remains disappointingly low at approximately 37%,” Ilse Molendijk, MD, from the department of gastroenterology and hepatology at Leiden University Medical Center in The Netherlands, told Healio Gastroenterology. “We performed a double-blind, placebo-controlled randomized dose-finding study addressing the use of allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) in the treatment of refractory [perianal fistulizing Crohn’s disease.”

Ilse Molendijk

Molendijk and colleagues randomly assigned five patients with refractory perianal fistulizing Crohn’s disease to receive injections of 1 x 107 MSCs, five to receive injections of 3 x 107 MSCs, five to receive injections of 9 x 107 MSCs and six to receive a placebo solution. Injections were administered into the wall of the curettage fistula around the trimmed and closed internal opening after surgery, and MSCs were sourced from the bone marrow aspirates of five healthy donors. Patients underwent physical examinations 6, 12 and 24 weeks later, and the primary outcome was fistula healing.

“Local administration of MSCs was found to be safe and feasible, resulting in a fistula healing rate of 85.7% up to 24 weeks after treatment with 3x107 MSCs [P = .06 vs. placebo],” Molendijk said.

At week 24, healing was also observed in 66.7% of the 1 x 107 dose group, 28.6% of the 9 x 107 dose group and 33.3% of the placebo group. The injections were well tolerated and no related adverse events occurred with any dose.

“Local treatment with 3 x 107 MSCs showed superior fistula healing compared with placebo, and lower MSC dose seemed superior to the use of a higher dose,” the researchers concluded.

David A. Schwartz

“Anti-TNF therapies have revolutionized the treatment of IBD. However, about one-third of patients with perianal fistula are primary nonresponders to anti-TNF agents,” Damian Garcia-Olmo, MD, from the department of surgery at the Autonomous University of Madrid, and David A. Schwartz, MD, from the Inflammatory Bowel Disease Center at Vanderbilt University Medical Center, wrote in a related editorial. “There is a need for other agents with different mechanisms of action for these patients.”

Stem cells “have demonstrated an excellent safety profile in several early phase clinical trials and hence should be considered as … potential therapeutic agents for refractory perianal fistulas in patients with [Crohn’s disease] as Molendijk [and colleagues] have proposed,” they added. “Despite the encouraging initial trials, the available information about long-term outcomes seems to be modest.” – by Adam Leitenberger

Disclosures: The researchers report no relevant financial disclosures. Garcia-Olmo reports he is a member of the scientific advisory board of Tygenix, and is an inventor in two patents related to cell products. Schwartz reports he is a consultant for Tygenix, AbbVie, Takeda, UCB and Janssen, and has received research funding from Abbvie and UCB.