Mesenchymal Stem Cell Injection in Crohn’s Disease Strictures: A Phase I–II Clinical Study

Abstract

Background and aim Mesenchymal stem cells (MSCs) have anti-inflammatory and anti-fibrotic properties and could be a potential therapy for Crohn’s Disease (CD) strictures. In this phase I–II pilot trial, we assessed safety and efficacy of local MSC injection to treat CD strictures. Methods CD patients with a short (less than 5 cm in length) non-passable stricture accessible by ileocolonoscopy were included. Allogenic bone-marrow derived MSCs were injected in the 4 quadrants of the stricture. Adverse events and clinical scores were evaluated at each followup visit while endoscopy and magnetic resonance enterography were performed at baseline, week (W)12 and W48. The main judgement criterion 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 W12. Second efficacy criteria included assessment of the stricture at W48 and evolution of clinical scores at W12 and W48. Results We performed 11 MSC injections in 10 CD patients (3 primary and 7 anastomotic strictures; 1 stricture injected twice). MSC injections were well tolerated but 4 hospitalizations for occlusion were reported. At W12, 5 patients presented a complete or partial resolution of the stricture (2 complete and 3 partial). Seven patients were re-evaluated at W48 (1 dilated, 1 operated, and 1 lost to follow-up) and 4 patients had a complete resolution. The evolution of clinical scores between W0, W12 and W48 was not statistically significant. Conclusion MSCs injection in CD stricture was well tolerated and may offer a benefit.

General consensus on multimodal functions and validation analysis of perinatal derivatives for regenerative medicine applications

“…Similarly, the application of allogeneic UC-MSC exhibited safety, feasibility, limited or no adverse effects, and led to the improvement of clinical symptoms. However, no significant changes in the levels of inflammatory cytokines in blood serum were detected ( Hossein-khannazer et al, 2021 ; Vieujean et al, 2022 ).…”

Prospective therapeutics for intestinal and hepatic fibrosis

“…In addition, clinical studies have demonstrated that autologous or allogeneic adipose‐derived MSCs exert promising therapeutic effects on anal fistulae, closely related to fibrosis 121,122 . In a recent phase I–II clinical study, local injections of MSCs were found to reverse intestinal fibrosis and resolve intestinal stenosis 123 . This effect was most likely dependent on their immunoregulatory effects and inhibition of TGF‐β signaling 124 demonstrating an exciting prospect of simultaneous anti‐inflammatory and anti‐fibrosis effects from MSC therapies.…”

“…121,122 In a recent phase I-II clinical study, local injections of MSCs were found to reverse intestinal fibrosis and resolve intestinal stenosis. 123 This effect was most likely dependent on their immunoregulatory effects and inhibition of TGF-β signaling 124 demonstrating an exciting prospect of simultaneous anti-inflammatory and anti-fibrosis effects from MSC therapies. EVs derived from MSCs may also regulate intestinal fibrosis through cargo loading.…”

Intestinal microecology-based treatment for inflammatory bowel disease: Progress and prospects

“…The results showed that clinical remission might be sustained in the long term and no apparent new safety signals were identified[ 78 ]. In the latest phase I-II pilot trial, local MSC injection may also help resolve CD strictures[ 79 ]. However, using MSCs to promote ulcer healing and repair the epithelial barrier has not been confirmed by clinical trials and more studies are awaited.…”