Department of Biology, Sa.C, Islamic Azad University, Sanandaj, Iran.
Abstract: (7 Views)
Umbilical cord-derived mesenchymal stem cells (UCMSCs) have emerged as one of the most promising cell sources in regenerative medicine, offering a unique combination of ethical accessibility, noninvasive procurement, low immunogenicity, rapid ex vivo expansion, genetic stability, and a potent paracrine secretome. This comprehensive review synthesizes current knowledge on the biological characteristics of UC-MSCs, including their origin, phenotypic and karyotypic stability, transcriptomic signatures, multilineage differentiation capacity, immunomodulatory properties, and tumorigenic safety profile. Furthermore, this article provides an in-depth analysis of the therapeutic potential of UCMSCs across a wide spectrum of clinical indications, encompassing musculoskeletal disorders, liver diseases, type 2 diabetes and its complications, premature ovarian failure, neurological conditions, pulmonary diseases, and immune-mediated disorders. Special emphasis is placed on recent clinical trial outcomes, safety data, and translational challenges. In addition, this review highlights the emerging paradigm of cell-free therapies, particularly UC-MSC-derived exosomes and extracellular vesicles (EVs), which recapitulate many of the therapeutic benefits of their parental cells while offering enhanced stability, reduced immunogenicity, superior safety profiles, and the ability to cross biological barriers such as the bloodbrain barrier. The molecular cargo of these nanovesicles—including diverse RNAs (mRNAs, miRNAs, IncRNAs, circRNAs) and bioactive proteins—mediates multifaceted effects including angiogenesis, anti-apoptosis, immunomodulation, and tissue regeneration. Despite the encouraging preclinical and early clinical data, successful translation to routine clinical practice faces significant obstacles, including protocol standardization, manufacturing scalability, regulatory approval, long-term safety evaluation, and therapeutic durability. This review concludes by discussing future directions, including biomaterialbased delivery systems, genetic engineering, personalized medicine approaches, and the integration of artificial intelligence and multi-omics strategies to optimize UC-MSC-based and exosomebased therapies. Collaborative interdisciplinary efforts are essential to overcome current challenges and realize the full therapeutic potential of UC-MSCs in revolutionizing regenerative medicine.