ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SU-OR04

Supramolecular Nanofibers Containing Arginine-Glycine-Aspartic Acid (RGD) Boost Therapeutic Efficacy of Extracellular Vesicles in Kidney Repair

Session Information

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.