{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:44:49Z","timestamp":1789469089639,"version":"build-2803163510"},"reference-count":173,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Immune disorders remain a major global health challenge, as conventional immunosuppressive therapies are often hampered by severe side effects and unsatisfactory long-term efficacy. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have emerged as a promising therapeutic modality for various immune disorders and balance immune homeostasis by regulating various immune cells and secreting anti-inflammatory mediators. We systematically review and synthesize preclinical and clinical evidence supporting UC-MSC treatment for major immune diseases, with graft-versus-host disease, systemic lupus erythematosus, inflammatory bowel disease, and rheumatoid arthritis being prime examples. Despite the promising therapeutic outcomes, therapeutic efficacy and large-scale clinical manufacturing of UC-MSC therapies are constrained by multiple challenges. This review also systematically examines the major translational bottlenecks for UC-MSCs in treating immune disorders, including cellular heterogeneity, non-uniform preparation standards, impaired homing and biodistribution, and insufficient long-term safety data. Finally, two main avenues for enhancing UC-MSC therapeutic potential are summarized, including optimized culture strategies, such as hypoxic preconditioning, cytokine priming, and three-dimensional spheroid culture, and genetic engineering. It is hoped that we will be able to gain a deeper understanding of the development of stable and scalable UC-MSC interventions for immune diseases.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1948742","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:33:23Z","timestamp":1789464803000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunomodulatory properties of umbilical cord mesenchymal stromal cells in immune disorders: immunoregulatory functions, therapeutic progress, and engineering strategies for enhanced efficacy"],"prefix":"10.3389","volume":"17","author":[{"given":"Chenglian","family":"Xie","sequence":"first","affiliation":[{"name":"Laboratory of Stem Cells and Regenerative Medicine, Qinghai University Affiliated Hospital","place":["Xining, Qinghai, 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