Utilizing Tumor-Derived Extracellular Microvesicles for Kidney Regeneration

Abstract

Abstract Background A comparative study was conducted to assess the potential of extracellular microvesicles (MVs) derived from mesenchymal stem cells (MSCs) and tumor cells in kidney regeneration using an experimental murine model of chronic kidney injury (CKI). Methods MVs were obtained from MSCs, L929 sarcoma, LLC carcinoma, or B16 melanoma cells. These MVs were then administered intravenously to CBA mice with CKI. Renal excretory function was evaluated based on serum concentrations of creatinine and fatty acid binding protein-1. Morphological changes in the kidneys were assessed histologically. Flow cytometry analysis was utilized to characterize T cells in spleens and renal cell infiltrates. Results The study revealed that both MSCs and MSC-derived MVs (MSC-MVs), as well as tumor-derived MVs (T-MVs), regardless of their origin, exhibited a comparable ability to improve both excretory function and the histological structure of the damaged kidney. Both MSC-MVs and T-MVs reduced the proportion of pro-inflammatory CD4 + CD44 + T cells in renal cell infiltrates and spleens of CKI mice. Furthermore, the MVs studied increased the numbers of natural CD4 + CD25 + FoxP3 + regulatory T cells in the spleen but not in renal cell infiltrates. Conclusions These findings suggest that T-MVs, similar to MSC-MVs, possess a universal capacity to stimulate kidney tissue restoration and provide anti-inflammatory immunomodulation of the kidney milieu.