Urine-Derived Stem Cells: Applications of Paracrine-Driven Regeneration and Functional Recovery in Multiorgan Systems

Stem cell therapy, a highly recognized approach in the field of regenerative medicine, is known for its potential to stimulate the self-healing process of the body using stem cells or their derivatives, in which urine-derived stem cells (USCs) stand out as a novel and promising tool in treating various diseases recently. USCs are widely believed to derive primarily from glomerular parietal epithelial cells and podocytes and can be readily isolated from urine. Owing to telomerase-associated self-renewal capacity, USCs proliferate efficiently in vitro, while their outstanding differentiation potential and paracrine effects support promising applications in tissue regeneration and functional recovery. The extracellular particles (EPs) of USCs, including various activity factors, exosomes, and other extracellular vesicles (EVs), play significant roles in the paracrine effects of USCs, which have gained recognition as pivotal factors in the therapeutic studies of USCs. USCs-EPs can affect on diseases in different organ systems through various mechanisms, in which cell differentiation, angiogenesis, and cell proliferation and migration are the three mainly affected functions. And the USCs-EPs may play dual roles based on different curative effects. Besides, the varied modification and encapsulation of USCs-EPs may promote their therapeutic effects. Up to now, USCs-EPs have been widely studied in multiorgan systems and are considered to be superior to USCs because of the rare risks of diverse genetic backgrounds, teratoma formation and immunogenicity. Although in the current preclinical stage, USCs-EPs represent a promising novel tool in stem cell therapy and warrant further exploration for their clinical potential.