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Abstract: FR-PO349

Proteomic Analysis of Acutely Injured Kidneys Following Treatment With Mesenchymal Stem Cells

Session Information

Category: Development‚ Stem Cells‚ and Regenerative Medicine

  • 500 Development‚ Stem Cells‚ and Regenerative Medicine

Authors

  • Erickson, Chris, University of Colorado, Denver, Colorado, United States
  • Soranno, Danielle, Indiana University, Bloomington, Indiana, United States
Background

Acute kidney injury (AKI) can result in renal fibrosis and kidney disease. Mesenchymal stem cells (MSC) have been studied as a potential treatment to mitigate renal damage from AKI. Proteomics can give insights into cell and tissue response by profiling changes to the extracellular matrix (ECM) following AKI. In this study we investigate changes to the kidney proteome following AKI and treatment with MSCs.

Methods

All procedures were IACUC approved. 8 week-old C57BL/6J male mice underwent bilateral ischemia-reperfusion AKI (clamp time 25 min). Animal groups were: AKI treated with: 1)MSC injected under renal capsule (subcap); 2)MSC injected IV; 3)MSC in hyaluronic acid hydrogels injected subcap; 4)No treatment; or 5)Sham AKI. After 3 months, mice were euthanized, kidneys harvested, processed for ECM extraction, and resultant renal tissue (N=5/group) were analyzed for proteomics by LC-MS/MS. Bioinformatics was performed on the resulting dataset. Statistical significance was determined by FDR corrected ANOVA p-value <0.05.

Results

MSC-treated mice did not cluster by proteomic analysis according to delivery method. Hierarchical clustering of the most expressed proteins showed three groups: 1)Sham AKI; 2)‘Recovered’ treated kidneys (RK); and 3)‘Not Recovered’ treated kidneys (NRK), which closely correlated with the untreated AKI group. NRKs showed high expression of fibrinogen, fibrillar collagens, and histones. The RK group showed attenuated expression of fibrinogens, collagens, and histones.

Conclusion

Our results showed increases in fibrinogen, fibrillar collagens, and histones in NRKs after AKI; whereas RKs showed lower levels of these proteins, indicating lower levels of fibrosis and preservation of ECM integrity. Further studies will investigate the mechanism of action of MSC therapy.

Funding

  • NIDDK Support