Exploring Porcine Precision-Cut Kidney Slices as a Model for Transplant-Related Ischemia-Reperfusion Injury
Abstract
:1. Introduction
2. Materials and Methods
2.1. Experimental Design
2.2. Animal Model
2.3. Cold Preservation
2.4. Precision-Cut Kidney Slices
2.5. Evaluation of Viability
2.6. Histological Analysis
2.7. Determination of Fungal Infection
2.8. Statistical Analysis
3. Results
3.1. HMP-O2 as Cold Preservation Results in Significant Higher PCKS Viability
3.2. Porcine PCKS Remain Viable up to 72 h
3.3. WME Provides the Most Beneficial Incubation Conditions
3.4. PCKS Remain Viable under Both Hypothermic and Normothermic Conditions
3.5. Amfotericine B Is Safe to Add to Prevent Fungal Infections
4. Discussion
4.1. Oxygenated HMP Provides an Excellent Foundation for Viable Porcine PCKS
4.2. WME Best Supports the Renal Metabolism of Porcine PCKS
4.3. Porcine PCKS Can Be Incubated under Both Hypo- and Normothermic Conditions
4.4. ATP as a Biomarker for Renal Tissue Viability
4.5. Advantages and Disadvantages of Porcine PCKS
4.6. Future Perspectives Porcine PCKS in Translation to NMP
4.7. Limitations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Correction Statement
Appendix A
Perfusate Composition: | |
Heparinized and leukocyte-depleted autologous blood | |
Red blood cells: | 360 mL |
Plasma: | 475 mL |
Amoxicillin/Clavulanic acid (1000 mg/200 mg) | 10 mG |
8.4% Sodium bicarbonate (B. Braun) | 15.25 mL |
5% Glucose (Baxter) | 12.50 mL |
Dexamethasone (Centrafarm) | 8.3 mG |
Mannitol (Baxter) | 10 mG |
Creatinine (Merck) | 135 mG |
Sodium nitroprusside (Merck) | 2.7 mG |
Aminoplasmal (B. Braun) | 90 mL |
Insulin (100 IU/mL) (Novorapid) | 0.186 mL |
250 µg/mL Amfotericine B (Fungizone) (Merck) | 1 mL |
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Experimental Group | Medium Composition |
---|---|
WME | Williams Medium E (1X) with GlutaMAX (WME) (Gibco) + 10 µG/mL ciprofloxacin (Fresenius Kabi, France) |
WME + Glucose | WME + 10 µG/mL ciprofloxacin + extra added D-(+)-glucose solution (Sigma-Aldrich, St. Louis, MO, USA) total end concentration 25 mM |
WME + Dextran40 | WME + 10 µG/mL ciprofloxacin + 25 µG/mL Amphotericin B + 3.5% Dextran40 (Sigma-Aldrich, St. Louis, USA) |
WME + Fungi (0.25) | WME + 10 µG/mL ciprofloxacin + 25 µG/mL Amphotericin B (Fungizone) (Merck) |
WME + Fungi (1) | WME + 10 µG/mL ciprofloxacin + 100 µG/mL Amphotericin B |
RPMI | Roswell Park Memorial Institute 1640 (RPMI) (Gibco) + 10 µG/mL ciprofloxacin + 11 mM D-(+)-glucose solution |
Blood | Diluted blood NMP perfusate (See Appendix A) |
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van Furth, L.A.; Leuvenink, H.G.D.; Seras, L.; de Graaf, I.A.M.; Olinga, P.; van Leeuwen, L.L. Exploring Porcine Precision-Cut Kidney Slices as a Model for Transplant-Related Ischemia-Reperfusion Injury. Transplantology 2022, 3, 139-151. https://doi.org/10.3390/transplantology3020015
van Furth LA, Leuvenink HGD, Seras L, de Graaf IAM, Olinga P, van Leeuwen LL. Exploring Porcine Precision-Cut Kidney Slices as a Model for Transplant-Related Ischemia-Reperfusion Injury. Transplantology. 2022; 3(2):139-151. https://doi.org/10.3390/transplantology3020015
Chicago/Turabian Stylevan Furth, L. Annick, Henri G. D. Leuvenink, Lorina Seras, Inge A. M. de Graaf, Peter Olinga, and L. Leonie van Leeuwen. 2022. "Exploring Porcine Precision-Cut Kidney Slices as a Model for Transplant-Related Ischemia-Reperfusion Injury" Transplantology 3, no. 2: 139-151. https://doi.org/10.3390/transplantology3020015