Therapeutic applications of human umbilical cord-derived mesenchymal stem cell secretome in chronic inflammatory diseases and cancer: A recent update

Chronic inflammatory disorders and cancer remain major global health challenges driven by persistent immune activation and tissue damage. The human umbilical cord-derived mesenchymal stem cell (hUC-MSC) secretome has emerged as a promising cell-free therapeutic alternative owing to its potent anti-inflammatory, immunomodulatory, and regenerative properties. Comprising of cytokines, chemokines, growth factors, and extracellular vesicles enriched with bioactive miRNAs, the hUC-MSC secretome exerts its effects primarily through paracrine signaling. For this review, relevant literature was collected from established databases, including ScienceDirect, PubMed, and Google Scholar, using key terms such as "hUC-MSC secretome," "chronic inflammation," "exosomes," "tumor microenvironment," and "preconditioning." The search focused on studies published within the last five years, emphasizing in vitro and in vivo preclinical studies, original research, and review articles. Only studies specifically exploring hUC-MSC-derived secretomes were included, whereas those addressing cell-based therapies or secretomes from other MSC sources were excluded. Cumulative findings indicate that the hUC-MSC secretome alleviates chronic inflammation by releasing anti-inflammatory cytokines such as IL-10 and TGF-β, as well as regulatory miRNAs such as miR-29a-3p, miR-100-5p, and miR-125b-5p, which act via key signaling pathways including PI3K/AKT, Wnt/β-catenin, and JAK/STAT. These mechanisms collectively mediate anti-inflammatory responses, suppress epithelial-mesenchymal transition, enhance chemosensitivity, and promote tissue repair. This review aims to consolidate the emerging evidence that positions the hUC-MSC secretome as a next-generation cell-free therapeutic strategy for chronic inflammatory diseases, including major cancers, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative disorders, while highlighting current limitations and strategies to enhance the therapeutic efficacy and clinical applicability of the hUC-MSC secretome.