Abstract: SU-OR04
Supramolecular Nanofibers Containing Arginine-Glycine-Aspartic Acid (RGD) Boost Therapeutic Efficacy of Extracellular Vesicles in Kidney Repair
Session Information
- AKI Mechanisms: Research Abstracts
October 25, 2020 | Location: Simulive
Abstract Time: 05:00 PM - 07:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Zhang, Chuyue, Chinese PLA General Hospital, Beijing, Beijing, China
- Wu, Jie, Chinese PLA General Hospital, Beijing, Beijing, China
- Wu, Lingling, Chinese PLA General Hospital, Beijing, Beijing, China
- Chen, Xiangmei, Chinese PLA General Hospital, Beijing, Beijing, China
Background
Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSC-EVs) have been recognized as a promising cell-free therapy for acute kidney injury (AKI), which avoids safety concerns associated with direct cell engraftment. However, low stability and retention of MSC-EVs have limited their therapeutic efficacy. RGD peptide binds strongly to integrins, which have been identified on the surface of MSC-EV membranes, yet RGD has not been applied to EV scaffolds to enhance and prolong bioavailability.
Methods
Here, we developed RGD hydrogels, which we hypothesized could augment MSC-EV efficacy against AKI.
Results
In vivo tracking of the EVs revealed that RGD hydrogels increased retention and stability of EVs. Upon intrarenal injection, EV-RGD hydrogels provided superior rescuing effects at functional, histopathological and molecular levels. Further analysis revealed that the presence of microRNA let-7a-5p in MSC-EVs served as a novel mechanism contributing to the reduced cell apoptosis and elevated cell autophagy in AKI.
Conclusion
RGD hydrogels boosted the therapeutic efficacy of let-7a-5p-containing-EVs in AKI repair. This study developed an RGD-scaffold to increase the EV integrin-mediated loading and in-turn improved therapeutic efficacy, therefore this strategy shed light on MSC-EVs application as cell-free treatment for potentiated efficiency.
RGD Hydrogels Boost Therapeutic Efficacy of Extracellular Vesicles in Kidney Repair. (A) The structure of the hydrogels. (B-C) RGD hydrogels enhanced the stability and retention of EVs. (D-H) RGD hydrogels improved the therapeutic efficacy of EVs at functional, histopathological and molecular levels. (I-L) Underlying mechanisms of let-7a-5p-containing-EVs protected against AKI.