Application of Human Umbilical Cord Mesenchymal Stem Cells and Their Derived Exosomes in Gastrointestinal Diseases

Gastrointestinal (GI) diseases are increasing in prevalence worldwide and represent a major public health burden. However, current treatments remain limited and are often associated with adverse effects, highlighting the need for innovative therapeutic strategies. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have emerged as promising candidates because of their anti-inflammatory, immunomodulatory, and regenerative properties. Accumulating evidence indicates that many of their therapeutic effects are mediated by extracellular vesicles, particularly hUC-MSC-derived exosomes (hUC-MSC-exos). This review first summarizes the composition and therapeutic mechanisms of hUC-MSCs and hUC-MSC-exos in GI diseases. We discuss in detail their roles in immune regulation, gut microbiota modulation, and metabolic regulation. Additionally, we highlight their potential as natural therapeutic agents and drug delivery vehicles, as well as recent engineering strategies designed to improve their therapeutic efficacy, stability, storage, and targeted delivery. We further summarize current clinical evidence. Despite encouraging preclinical findings, clinical evidence remains limited, and their effects in gastrointestinal tumors are context-dependent, with both tumor-promoting and tumor-suppressive activities reported. Further studies are needed to characterize the functional components of hUC-MSCs and hUC-MSC-exos and to clarify their effects on gastrointestinal tumors through rigorous in vivo investigations.