Biological Nanotherapeutics Derived From Human Umbilical Cord Mesenchymal Stem Cells: Mechanisms and Translational Potential in Multisystem Therapies for Regeneration and Oncology

Ruirui Zhang,1,2,* Zhipeng Xu,3,* Shijie Xu,1 Rong Li,1 Hui Qian1 1Jiangsu Province Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, People’s Republic of China; 2Department of Anatomy, School of Medicine, Jiangsu University, Zhenjiang, 212013, People’s Republic of China; 3Department of Urology, Affiliated People’s Hospital of Jiangsu University, The First People’s Hospital of Zhenjiang, Zhenjiang, Jiangsu, 212002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruirui Zhang; Hui Qian, Email [email protected]; [email protected]: Extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hucMSCs-EVs) represent a promising cell-free therapeutic strategy in regenerative medicine and oncology. These vesicles exhibit low immunogenicity, are non-invasively sourced, and possess multiple regenerative properties. This review examines the biogenesis of EVs and distinctive features of hucMSCs-EVs compared to other MSC-derived EVs. We explore their molecular mechanisms and preclinical efficacy across multiple organ systems, including nervous, locomotor, respiratory, circulatory, digestive, urinary, reproductive, and hormonal. HucMSCs-EVs demonstrate a dual role: promoting tissue repair through immunomodulation, angiogenesis, and anti-apoptosis in regenerative contexts, while exerting microenvironment-dependent pro- or anti-tumor effects in oncology. Despite promising preclinical results, clinical translation requires overcoming challenges such as standardized production, delivery optimization, and safety evaluation. As multifunctional biological nanotherapeutics, hucMSCs-EVs show transformative potential for treating multisystem diseases. However, their universal applicability is constrained by heterogeneity, biodistribution limitations, and environment-dependent efficacy. Future work should focus on scalable manufacturing, targeted delivery strategies, and rigorous clinical trials to realize their full therapeutic potential. Keywords: human umbilical cord mesenchymal stem cells, hucMSCs, extracellular vesicles, EVs, multisystem therapeutics, regenerative medicine, cancer therapy, biogenesis, translational challenges