MO352: The Effect and Mechanism of Renal Targeted Delivery of MSC Exosomes in the Treatment of AKI

Abstract

Abstract BACKGROUND AND AIMS AKI occurs in ∼15% hospitalized patients and over 50% intensive care unit patients. However, effective therapeutic strategies for AKI are urgently needed. The exosomes derived from mesenchymal stem cells (MSC-exos) have achieved great focus as a cell-free therapy. As foremost metabolic organs, MSC-exos mainly collect in the liver and spleen. More attention should be considered how to induce more exosomes targeted to the injured kidney. In addition, the potential role of MSC-exos in injured kidney and the underlying mechanisms still need further research. METHOD Transmission electron microscopy, western blotting and nanoparticle tracking analysis were used to identify the properties of human umbilical cord mesenchymal stem cells (hucMSCs) derived exosomes. Kidney targeting peptide was chosen by the IVIS spectrum imaging system. Moreover, kidney targeting peptide (peptide-CGA) and CD63 targeting peptide were loaded to the MSC-exos by co-incubated (CGA-exos). Flow cytometry and immunofluorescence staining were utilized to confirm this. IVIS spectrum imaging system was used to assess MSC-exos distribution in vivo. RESULTS In vivo imaging showed that Peptide-CGA was efficiently homing to the ischemic kidney and predominantly accumulated in proximal tubules. Further Immunoprecipitation study showed that Peptide- CGA treatment group produced a specific stripe in silver staining compared with other groups. CGA-exos was successfully constructed. MSC-exos could alleviate murine ischemic kidney injury and reduced the renal tubules injury. Furthermore, in vivo imaging showed CGA-exos treatment group could attract more MSC-exos into the injured kidney, and its therapeutic effect was significantly better than that of the MSC-exos treatment group. without causing significant organ side effects. CONCLUSION Novel kidney targeting MSC-exos was constructed. It exhibited a preferential tendency to injured kidney and was localized to proximal tubules in AKI. We demonstrate that MSC-exos ameliorate ischemic AKI. But its further mechanisms need more insight. All in all, this highlights the potential of MSC-exos as a promising therapeutic strategy for AKI.