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Review
. 2025 Jul 21;16(1):393.
doi: 10.1186/s13287-025-04523-y.

The therapeutic potential of mesenchymal stem cells in intestinal diseases: from mechanisms to clinical translation

Jia-Zhi Yang #  1 , Li-Yan He #  1 , Xian-Zhou Lu  2
Affiliations
Review

The therapeutic potential of mesenchymal stem cells in intestinal diseases: from mechanisms to clinical translation

Jia-Zhi Yang et al. Stem Cell Res Ther. .

Abstract

Current therapeutic interventions for intestinal pathologies, including anti-inflammatory agents, immunosuppressants, and surgical procedures, frequently incur substantial adverse effects, elevated recurrence rates, and suboptimal tissue regeneration. Cellular therapy has emerged as a paradigm-shifting strategy, capitalizing on regenerative potential and immunomodulatory properties. Mesenchymal stem cells (MSCs), distinguished by their potent immunoregulatory capacity and multipotent differentiation plasticity, have recently demonstrated remarkable therapeutic promise in inflammatory bowel disease (IBD), ischemia-reperfusion injury, oncological interventions, and radio-chemotherapy-induced complications. This systematic review critically evaluates MSC biological characteristics, clinical translation progress, and cutting-edge advancements in tissue engineering applications. Mechanistic insights into MSC-mediated intestinal repair are elucidated, with particular emphasis on emerging evidence suggesting MSC-derived exosomes may modulate ZBP1-associated H3K27 acetylation to attenuate intestinal epithelial apoptosis-a novel epigenetic regulatory axis for gastrointestinal restitution. Future translational trajectories and clinical implementation challenges are comprehensively discussed.

Keywords: Cell and Tissue Engineering; Exosomes; Intestinal Epithelium; Stem Cells; ZBP1.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Characteristics of intestinal MSCs. a Guided by the chemokine stromal cell-derived factor-1 (SDF-1), MSCs migrate across epithelial barriers and accumulate in target tissues; b MSCs differentiate into intestinal stem cells (ISCs), which subsequently generate intestinal epithelial cells, with the Wnt/β-catenin signaling pathway identified as a key regulatory mechanism in this process; c Exosomes derived from MSCs not only act through the Snail/Claudins signaling pathway but also by restoring gut microbiota diversity, thereby protecting the integrity of the intestinal barrier; d MSCs inhibit T cell proliferation by secreting cytokines and promote the differentiation of regulatory T-cell (Treg), thereby alleviating inflammatory responses
See this image and copyright information in PMC

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