Mesenchymal stem cells (MSCs) are emerging as a promising regenerative and immunomodulatory therapy in gastroenterology, supported by encouraging clinical and experimental data.
In inflammatory bowel disease (IBD), local MSC injection has become an established option for perianal fistulizing Crohn’s disease, achieving long-term remission with a favorable safety profile. A meta-analysis of 25 studies (596 patients) reported combined remission rates of approximately 58% at 6 months, demonstrating superiority over placebo, with similar efficacy between adipose- and bone marrow–derived MSCs (Guillo et al., 2025). Real-world data on adipose-derived MSCs (darvadstrocel) show remission rates of 78% at 26 weeks and 62% at 52 weeks, alongside high patient satisfaction and low serious adverse events (Bacsur et al., 2025).
In ulcerative colitis refractory to standard therapies, intravenous umbilical cord–derived MSCs achieved 73% clinical response and 42% clinical remission at 2 months, accompanied by endoscopic healing, reduced pro-inflammatory cytokines, and increased anti-inflammatory IL-10, without serious safety concerns (Jiang et al., 2024).
In chronic liver disease, pooled randomized trials show that MSC infusions significantly improve MELD scores, albumin levels, and coagulation parameters, while reducing hepatic encephalopathy and gastrointestinal bleeding events. Fever was the only consistently reported mild adverse effect (Liu et al., 2022).
Systematic reviews indicate that MSCs and their secretome exert broad anti-inflammatory, anti-apoptotic, and pro-regenerative effects. They improve epithelial barrier integrity, stimulate intestinal stem and epithelial cell proliferation, and modulate dysregulated gut immunity and microbiota (Saadh et al., 2023; Xiang et al., 2022; Shi et al., 2022).
Beyond whole-cell therapy, MSC-derived extracellular vesicles (EVs/exosomes) reproduce many of these benefits — reducing intestinal inflammation, promoting mucosal repair, and restoring intestinal homeostasis — while being less immunogenic and easier to standardize and store. This positions EVs as a promising next-generation, cell-free therapeutic strategy for gastrointestinal disorders.
| Indication / setting | MSC type & route | Main positive outcomes | Citations |
|---|---|---|---|
| Perianal fistulizing Crohn’s disease | Local injection of adipose- or bone marrow–derived MSCs | ~58% combined remission at 6 months; superior to placebo; good safety | (Ko et al., 2021; Guillo et al., 2025; Qiao et al., 2024; Bacsur et al., 2025) |
| Refractory ulcerative colitis | IV umbilical cord MSCs | 73% clinical response, 42% remission at 2 months; sustained benefit at 6 months; cytokine normalization; no serious AEs | (Hosseini-Asl et al., 2020; Jiang et al., 2024) |
| Chronic liver disease / ACLF, cirrhosis | Bone marrow and umbilical cord MSCs, IV or intra-arterial | Improved MELD, albumin, coagulation; reduced encephalopathy and GI bleeding; no serious safety issues | (Liu et al., 2022) |
| Experimental IBD and GI injury models | Various tissue-derived MSCs and MSC EVs | Reduced inflammation and oxidative stress, enhanced epithelial regeneration and barrier function, improved survival | (Yang et al., 2025; Saadh et al., 2023; Didamoony et al., 2023; Clua-Ferré et al., 2024; Xiang et al., 2022; Shi et al., 2022; Payushina et al., 2022) |
Figure 1: Representative successful uses of MSC therapy in GI diseases.
MSC extracellular vesicles (EVs)/exosomes reproduce many benefits of cells with lower immunogenicity and tumor risk and easier storage, and show efficacy in models of COPD, asthma, fibrosis and ARDS (Abbaszadeh et al., 2022; Zhang et al., 2025; Yiming et al., 2022; Mohammadipoor et al., 2018). Secretome based approaches are emerging as favored “cell free” therapeutics (Fernández-Francos et al., 2021; Yiming et al., 2022; Mohammadipoor et al., 2018).
Across >100 pulmonary clinical trials, IV MSCs (often bone marrow or umbilical cord derived) appear safe, but effects on lung function, symptoms and survival are modest and inconsistent so far (Cruz & Rocco, 2020; Wang et al., 2021; Chen et al., 2021; Antoniou et al., 2018). Critical gaps include best source (UC MSCs may be superior in ARDS), dose, route, timing, and need for repeated dosing or genetic/conditioning strategies to boost potency (Cruz & Rocco, 2020; Fernández-Francos et al., 2021; Wang et al., 2021; Regmi et al., 2024). In pulmonology, MSCs and their EVs are promising tools for inflammatory and fibrotic lung diseases, especially ARDS, COPD, asthma and IPF. For now they remain experimental: safe in early trials, clearly effective in animal models, but with human efficacy still to be proven in large, well designed studies.
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Bacsur, P., Shaham, D., Serclova, Z., Resál, T., Farkas, B., Sarlós, P., Miheller, P., Maharshak, N., Zemel, M., Shirit, A., Bálint, A., Fábián, A., Bor, R., Bősze, Z., Ivány, E., Szepes, Z., Farkas, K., Tóth, I., Lázár, G., Vlkova, K., Tremerova, A., Zuskova, P., Ábrahám, S., & Molnár, T. (2025). P0821 Effectiveness and safety of mesenchymal stem cell treatment in fistulizing Crohn’s disease: predictors of treatment success. Journal of Crohn's and Colitis. https://doi.org/10.1093/ecco-jcc/jjae190.0995