In Vivo Electroporation-Mediated, Intrahepatic Alpha1 Antitrypsin Gene Transfer Reduces Pulmonary Emphysema in Pallid Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plasmid
2.2. Pallid Mice
3. Electroporation-Mediated Gene Transfer to the Liver
4. Assessment
4.1. Lung Function
4.2. Tissue Collection
4.3. Histology and Microscopy
4.4. Stereological Analysis
4.5. Sirius Red Staining
4.6. Immunofluorescence Staining
4.7. Liver Homogenization
4.8. ELISA
4.9. Myeloperoxidase Activity
4.10. Measurement of Liver Injury
5. Statistics
6. Results
6.1. Lung Function Is Improved after Intrahepatic Electroporation-Mediated AAT Gene Transfer
6.2. Stereological Analysis Reveals Improved Lung Architecture after AAT Gene Transfer
6.3. AAT Gene Transfer by Electroporation Did Not Induce Liver Injury
6.4. Lung Neutrophil Burden Is Reduced after AAT Gene Transfer
7. Discussion
8. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Parameters | WT (Wildtype) | Pallid Mice | Empty Vector | hAAT Plasmid |
---|---|---|---|---|
Static Compliance (mL/cmH2O) | 0.068 ± 0.004 | 0.0767 ± 0.004 | 0.0749 ± 0.001 | 0.064 ± 0.002 |
Total Lung capacity (A) (mL) | 0.80 ± 0.04 | 0.95 ± 0.03 | 0.99 ± 0.06 | 0.73 ± 0.01 |
Hysteresis (cmH2O/mL) | 3.29 ± 0.34 | 4.70 ± 0.31 | 5.50 ± 0.13 | 3.66 ± 0.40 |
AUC (area under curve) (mL/cmH2O) | 0.39 ± 0.06 | 0.72 ± 0.10 | 0.73 ± 0.11 | 0.47 ± 0.06 |
k (curvature of the upper portion of the deflation limb of the pressure volume (PV) curve) | 0.11 ± 0.006 | 0.13 ± 0.004 | 0.143 ± 0.0005 | 0.12 ± 0.004 |
Parameters | WT | Pallid Mice | Empty Vector | hAAT Plasmid |
---|---|---|---|---|
Surface Area (cm2) | 238.2 ± 22.76 | 187.6 ± 8.43 | 154.4 ± 16.09 | 229.6 ± 7.94 |
Mean liner intercept (LM) (µM) | 40.9 ± 1.68 | 52.38 ± 1.42 | 58.68 ± 3.69 | 45.79 ± 0.33 |
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Sutter, M.A.; Cremona, T.P.; Nita, I.; Cavarra, E.; Lungarella, G.; Lewis, E.C.; Schittny, J.C.; Geiser, T.; Gazdhar, A. In Vivo Electroporation-Mediated, Intrahepatic Alpha1 Antitrypsin Gene Transfer Reduces Pulmonary Emphysema in Pallid Mice. Pharmaceutics 2020, 12, 793. https://doi.org/10.3390/pharmaceutics12090793
Sutter MA, Cremona TP, Nita I, Cavarra E, Lungarella G, Lewis EC, Schittny JC, Geiser T, Gazdhar A. In Vivo Electroporation-Mediated, Intrahepatic Alpha1 Antitrypsin Gene Transfer Reduces Pulmonary Emphysema in Pallid Mice. Pharmaceutics. 2020; 12(9):793. https://doi.org/10.3390/pharmaceutics12090793
Chicago/Turabian StyleSutter, Marco A., Tiziana P. Cremona, Izabela Nita, Eleonora Cavarra, Giuseppe Lungarella, Eli C. Lewis, Johannes C. Schittny, Thomas Geiser, and Amiq Gazdhar. 2020. "In Vivo Electroporation-Mediated, Intrahepatic Alpha1 Antitrypsin Gene Transfer Reduces Pulmonary Emphysema in Pallid Mice" Pharmaceutics 12, no. 9: 793. https://doi.org/10.3390/pharmaceutics12090793
APA StyleSutter, M. A., Cremona, T. P., Nita, I., Cavarra, E., Lungarella, G., Lewis, E. C., Schittny, J. C., Geiser, T., & Gazdhar, A. (2020). In Vivo Electroporation-Mediated, Intrahepatic Alpha1 Antitrypsin Gene Transfer Reduces Pulmonary Emphysema in Pallid Mice. Pharmaceutics, 12(9), 793. https://doi.org/10.3390/pharmaceutics12090793