Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) that often leads to fibrotic intestinal strictures, narrowing the intestinal lumen and causing obstruction. Traditional approaches, including steroid injections, anti-TNF biologics, endoscopic balloon dilation (EBD), or surgical resection, provide only temporary relief and carry risks of recurrence or complications.
Recent research has highlighted the regenerative and anti-fibrotic potential of Mesenchymal Stem Cells (MSC Stem Cells). These cells exhibit strong immunomodulatory, anti-inflammatory, and tissue-repairing effects, offering new hope for patients with treatment-resistant Crohn’s disease.
A landmark clinical investigation conducted by Vieujean et al. (2022) at the University Hospital of Liège, Belgium, evaluated the safety and efficacy of localized MSC injections in Crohn’s strictures. This study represents one of the first phase I–II trials to explore direct intraluminal MSC delivery as a targeted approach for managing intestinal fibrosis.
Study Design and Methodology
The trial included 10 adult patients (11 MSC injections in total) suffering from non-passable Crohn’s strictures shorter than 5 cm, accessible by ileocolonoscopy. These patients were refractory to conventional or biologic therapies, including azathioprine, methotrexate, infliximab, vedolizumab, and ustekinumab.
The research team used allogeneic bone marrow–derived MSC Stem Cells prepared at the Laboratory of Cell and Gene Therapy (CHU of Liège). A total of 3 × 10⁷ MSCs were injected into four quadrants of the submucosal layer surrounding each stricture, using an endoscopic approach under expert supervision.
Follow-ups were conducted at Weeks 12 and 48, with endoscopic and magnetic resonance enterography (MRE) evaluations. The primary endpoint was complete or partial resolution of the stricture at 12 weeks, while secondary endpoints included long-term structural and clinical improvement.
Results
- Safety Profile
The MSC Stem Cells injections were well tolerated. No patients developed abscesses, perforations, or new fistulas. A few hospitalizations for obstruction were recorded, mainly due to pre-existing fibrosis rather than adverse MSC effects. This confirms the short-term safety of local MSC therapy, consistent with previous findings from perianal fistula and luminal Crohn’s studies.
- Efficacy Outcomes
- Week 12 Results: Five patients showed significant improvement, with two complete and three partial stricture resolutions.
- Week 48 Results: Four patients achieved full resolution, verified through endoscopy and MRE imaging.
- Long-Term Findings: Disappearance of T2 submucosal edema in responders indicated a reduction in inflammation and early fibrotic reversal.
Although statistical changes in Crohn’s Disease Activity Index (CDAI) and inflammatory markers were not significant, the reduced need for surgical or endoscopic re-intervention (only 20% of patients required further dilation or resection) suggested clinical benefit beyond standard therapy.
Mechanisms of Action
Anti-Inflammatory and Immunomodulatory Effects
MSC Stem Cells release cytokines and growth factors that suppress excessive immune activity, reducing inflammation that drives fibrosis. These include IL-10, TGF-β, and PGE2, which collectively rebalance immune signaling and promote healing.
Anti-Fibrotic Activity
The study reinforced evidence that MSC Stem Cells help inhibit fibrosis by regulating TGF-β, collagen remodeling, and extracellular matrix (ECM) deposition. MSC-secreted proteins such as Hepatocyte Growth Factor (HGF) and TSG-6help soften scar tissue and reduce fibroblast overactivation. Experimental models confirm that MSC Stem Cells can reverse established intestinal fibrosis, reducing fibrogenic cytokines like IL-1β, IL-6, and IL-13, while enhancing anti-fibrogenic IL-10 production.
Tissue Regeneration
MSC Stem Cells promote epithelial repair and angiogenesis in damaged intestinal mucosa. Their paracrine signaling facilitates myofibroblast regulation, reducing muscular hypertrophy and promoting smoother luminal passage.
Clinical Implications
The study demonstrates that local MSC injection is safe and potentially effective for Crohn’s strictures a chronic challenge where anti-inflammatory drugs and biologics often fail.
At Vega Stem Cell similar regenerative concepts are applied clinically using Umbilical Cord–Derived Mesenchymal Stem Cells (UC-MSC Stem Cells), which share and even surpass the regenerative capabilities of bone marrow MSC Stem Cells. UC-MSC Stem Cells provide:
- Stronger anti-inflammatory and anti-fibrotic action.
- Non-invasive sourcing and high expansion potential.
- No immune rejection risk, even in allogeneic applications.
For patients suffering from Crohn’s disease, ulcerative colitis, or bowel fibrosis, UC-MSC therapy aims to:
- Decrease intestinal inflammation and scarring.
- Improve gut motility and absorption.
- Reduce dependence on long-term steroids or immunosuppressants.
Limitations and Future Directions
Although promising, this trial’s small sample size and lack of a control group limit definitive conclusions. Future research should include:
- Larger, randomized controlled trials.
- Exploration of UC-MSC Stem Cells and exosome-based treatments for fibrosis reversal.
- Combination approaches pairing EBD with MSC therapy for synergistic outcomes.
The authors suggest that MSC-enhanced EBD may prevent re-scarring and extend remission durations an exciting avenue for future regenerative gastroenterology.
Conclusion
This phase I–II study provides compelling evidence that Mesenchymal Stem Cell therapy offers a safe and potentially regenerative option for Crohn’s disease strictures, combining anti-inflammatory, anti-fibrotic, and reparative mechanisms. With growing global evidence, UC-MSC-based regenerative therapy may soon become a cornerstone in managing complex gastrointestinal diseases like Crohn’s, reducing surgery dependency and restoring patients’ quality of life.
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Reference
Vieujean S, Loly JP, Boutaffala L, et al. (2022). Mesenchymal Stem Cell Injection in Crohn’s Disease Strictures: A Phase I–II Clinical Study. Journal of Crohn’s and Colitis, 16(3), 506–510. DOI: 10.1093/ecco-jcc/jjab154.