Elucidation of the biological functions of extracellular vesicles (EVs) and their potential roles in physiological and pathological processes is an expanding field of research. In this study, we characterized USC–derived EVs and studied their capacity to modulate the human immune response in vitro. We found that the USC–derived EVs are a heterogeneous population, ranging in size from that of micro–vesicles (150 nm–1 μm) down to that of exosomes (60–150 nm). Regarding their immunomodulatory functions, we found that upon isolation, the EVs (60–150 nm) induced B cell proliferation and IgM antibody secretion. Analysis of the EV contents unexpectedly revealed the presence of BAFF, APRIL, IL–6, and CD40L, all known to play a central role in B cell stimulation, differentiation, and humoral immunity. In regard to their effect on T cell functions, they resembled the function of mesenchymal stem cell (MSC)–derived EVs previously described, suppressing T cell response to activation. The finding that USC–derived EVs transport a potent bioactive cargo opens the door to a novel therapeutic avenue for boosting B cell responses in immunodeficiency or cancer.

Delivering hydrophobic molecules through the intestine can be challenging due to limited cargo solubility and the harsh biochemical environment of the stomach. Here, we show that a protein-based nanocarrier system based on the abundant protein histone and the natural cross-linker genipin can deliver hydrophobic cargos, such as dyes and therapeutic molecules, through the gastrointestinal tract. Using hydrophobic near-infrared dyes as model cargos, a panel of potential protein carriers was screened, and histone was identified as the one with the best loading capability. The resulting nanoparticles had a positive ζ potential and were mucoadhesive. Cross-linking of the amine-rich nanocarrier with genipin was particularly effective relative to other proteins and increased the stability of the system during incubation with pepsin. Cross-linking was required for successful delivery of a hydrophobic dye to the colon of mice after oral gavage. To assess the platform for therapeutic delivery, another hydrophobic model compound, curcumin, was delivered using cross-linked histone nanoparticles in a murine colitis model and significantly alleviated the disease. Taken together, these results demonstrate that histone is a cationic, mucoadhesive, and cross-linkable protein nanocarrier that can be considered for oral delivery.

The interplay between mesenchymal stem cells (MSCs) and immune cells has been studied for MSCs isolated from different tissues. However, the immunomodulatory capacity of urine stem cells (USCs) has not been adequately researched. The present study reports on the effect of USCs on peripheral blood lymphocytes. USCs were isolated and characterized before coculture with resting and with anti-CD3/CD28 bead stimulated lymphocytes. Similarly to bone marrow mesenchymal stem cells (BM-MSCs), USCs inhibited the proliferation of activated T lymphocytes and induced their apoptosis. However, they also induced strong activation, proliferation, and cytokine and antibody production by B lymphocytes. Molecular phenotype and supernatant analysis revealed that USCs secrete a range of cytokines and effector molecules, known to play a central role in B cell biology. These included B cell-activating factor (BAFF), interleukin 6 (IL-6) and CD40L. These findings raise the possibility of an unrecognized active role for kidney stem cells in modulating local immune cells.