Abstract: PO0627
Administration of Mesenchymal Stromal Cell-Derived Exosomes Is an Effective Rescue Therapy for Progressive AKI in Rats
Session Information
- Development, Stem Cells, and Regenerative Medicine
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 500 Development, Stem Cells, and Regenerative Medicine
Authors
- Gooch, Anna, SymbioCellTech, Salt Lake City, Utah, United States
- Westenfelder, Christof, University of Utah Hospital, Salt Lake City, Utah, United States
Background
Preclinical and clinical studies have shown Mesenchymal Stem Cells (MSCs) to be effective for prevention of AKI [NCT00733876]. Yet studies where MSCs are given 48 hrs. post-insult, a time at which most patients with severe AKI are diagnosed and when no rescue therapy is available, show them to be ineffective or even damaging due to compromised renal blood flow in capillary beds, where introduction of large cells has the potential to cause further deterioration of renal function [NCT01602328]. While MSCs’ renoprotection is largely due to their release of beneficial cytokines and exosomes, their potential negative impact on renal blood flow is a concern. Administration of MSC-derived exosomes is known to exert beneficial effects that are similar to those of the parent cells. We hypothesized that since MSC-derived exosomes can prevent AKI, their small size and ability to move through the microvasculature might allow them to also be an effective rescue therapy for late stage AKI where MSCs are ineffective.
Methods
MSCs from Sprague Dawley (SD) rats were used. Their purified exosomes were characterized for size by nanoparticle tracking analysis, protein concentration, gene expression of relevant markers, FACS (CD44 and CD29), and rtPCR.
I/R AKI (50-52 min bilateral renal pedicle clamp) was induced in 3 groups of SD rats (6-8/group). SCr was assessed at baseline, Days (D) 1 and 2. If the SCr value on D2 was greater than that on D1, then on D3, rats were given i.a. either 1 ml of Vehicle, 4x10e10, or 2x10e6 ASCs.
Studied Endpoints: SCr at Days 0-9; survival and renal injury.
Results
In contrast to what is found when MSCs are administered to rats immediately upon reflow, when administered to rats 48 hrs post-I/R AKI, 2x10e6 MSCs prove ineffective at ameliorating injury, while MSC-derived exosomes significantly and sustainably improve renal function by D5 post-injury.
Conclusion
MSC-derived exosome therapy administered 2 days post-insult, when renal blood flow is compromised, but also when most clinical instances of AKI are diagnosed, is superior to MSC therapy for rescue of AKI, likely due to the mirrored paracrine content, but significantly smaller size of exosomes compared to MSCs.
Our results support the hypothesis that MSC-derived exosomes could be used as a rescue therapy for non-spontaneously recovering AKI.
Funding
- Commercial Support –