Abstract :
[en] Intestinal fibrosis is a common complication of Crohn's disease (CD) leading to progressive bowel stricture formation. Mesenchymal stem cells (MSCs), known for their immunomodulatory, anti-inflammatory and anti-fibrotic properties, could be a potential therapy in this frequently fibro-inflammatory condition.
In this phase I–II open-label pilot trial, we aimed to assess safety and efficacy of local MSCs injection in CD strictures. CD patients with a short (less than 5 cm in lengh) non-passable stricture, accessible by ileocolonoscopy, but without intestinal obstruction, fistulas, or abscess, were included. A total of 3X107 allogenic bone-marrow derived MSCs were equally injected in the 4 quadrants of the strictured bowel wall during an ileocolonoscopy. Adverse events and clinical scores (Crohn Disease Activity Index, Short Health Scale and Crohn Disease Obstructive Score) were evaluated at each follow-up visit (at week (W) 4, 12, 24 and 48) while endoscopy and magnetic resonance enterography (MRE) were performed at baseline, W12 and W48. The main judgement criteria for efficacy was the complete (defined by the ability to pass the ileocolonoscope) or partial (defined by a diameter increase) resolution of the stricture at 12 weeks. Second efficacy criteria included complete or partial resolution of the stricture at 48 weeks as well as the evolution of clinical scores at W12 and W48.
Between 2018 and 2020, we performed 11 local MSCs injections in 10 CD patients (6 females; aged to 38-65 years; median 45 years old; 70% were smoker). The strictures’ (3 primary, 7 anastomotic; 1 stricture injected twice) location was as follows: 7 at an ileo-colonic or ileo-rectal anastomosis, 1 colonic and 2 of the ileocecal valve. No patient developed abscess or fistula in the follow-up. One patient had actually a small intestinal fistula at baseline (not diagnosed by the routine imaging report but disclosed by the central reading) which remained stable. A total of 5 hospitalizations for occlusion were reported (2 secondary to a different stricture than the injected one) leading to a surgical resection for one patient and an endoscopic dilatation for another one. At 12 weeks, 5 patients (45%) presented a stricture improvement with a complete resolution for 2 and a partial resolution for 3. Of the 11 MSCs injections, 6 strictures were re-evaluated at week 48 (2 patients still undergoing follow-up, 1 operated, 1 dilated, and 1 lost to follow-up), 4 patients had a complete resolution. The evolution of clinical scores between weeks 0, 12 and 48 was not statistically significant and MSCs injection did not significantly modify the stricture characteristics analysed by MRE, except the disappearance of T2 submucosal oedema in two endoscopic responders.
Local MSCs injection in non-passable CD stricture was well tolerated over the short term although several occlusions occured in the follow-up indicating insufficient therapeutic effect in thoses cases. Combining the effects of MSCs with the proven effect of endoscopic balloon dilatation could possibly improve the outcome of CD stricture.
