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Abstract: SA-PO020

Mesenchymal Stromal Cells (MSCs) Exposed to Interferon Gamma (INFγ) Secrete Exosomes (Exos) With a More Potent Renoprotective Profile Than Unexposed Cells

Session Information

  • Bioengineering
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Gooch, Anna, SymbioCellTech, Salt Lake City, Utah, United States
  • Skliar, Mikhail, University of Utah, Salt Lake City, Utah, United States
  • Chowdhury, Sabiha Sultana, SymbioCellTech, Salt Lake City, Utah, United States
  • Westenfelder, Christof, SymbioCellTech, Salt Lake City, Utah, United States
Background

Preclinical and clinical studies have shown 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]. MSCs’ renoprotection is mediated by their paracrine release of anti-inflammatory and trophic cytokines and their Exos. The beneficial paracrine profile of MSCs can be enhanced through exposure to INFγ. Exos signal, post uptake by target cells, through the lateral transfer of mRNAs, miRNAs, DNA, proteins, and lipids. Others have shown that MSC-derived Exos can prevent AKI. We have found that their small size and ability to move through the compromised renal microvasculature allows them to provide effective rescue therapy for late-stage AKI. We hypothesized that priming of MSCs with INFγ would result in the release of Exos enriched in immune modulatory and other beneficial cargo compared to those not so primed, and thus provide a potentially more potent biotherapy for AKI.

Methods

12 sets of human MSCs were cultured to 70% confluence. Serum was removed from the medium, and 6 were exposed overnight to 10ng/ml INFγ (Expt), and the other 6 to vehicle (Control). Exos were isolated from each of the 12 sets of medium. Expt and Control Exos were characterized and compared for size and number (Nanosite), mRNA (rtPCR) and miRNA (Rosalind) content.

Results

The number of Exos did not vary between Expt and Control groups. Expt Exos were slightly larger than Controls (163.2±4.1 vs 134.1±7.6 nm, respectively). Expt Exos’ cargo showed significantly increased immune modulatory mRNA, specifically IDO-1, CCL8, CXCL9, CXCL10 and PD-L1 vs Control. Expt Exos showed significant increases in 4 miRNAs associated with anti-inflammatory pathways.

Conclusion

Exposure of MSCs to INFγ results in release of Exos that carry significantly greater immune-modulatory and anti-inflammatory cargo, factors that are known to confer renoprotection. We predict such Exos to have enhanced renoprotective ability, which is currently being assessed.

Funding

  • Commercial Support