Humanized NSG Mouse Models as a Preclinical Tool for Translational Research in Inflammatory Bowel Diseases
Abstract
:1. Introduction
2. Results
2.1. The NSG-UC Mouse Model
2.1.1. Pathological Manifestations
2.1.2. Characterization of Cells Involved in Inflammation
2.1.3. Fibrotic Alterations of the Colon
2.1.4. Testing of Therapeutics in the NSG-UC Mouse Model
2.2. The NSG-CD Mouse Model
3. Discussion
4. Materials and Methods
4.1. Isolation of PBMCs and Engraftment
4.2. Study Protocol
4.3. Clinical Activity Score
4.4. Macroscopic Colon Score
4.5. Histological Analysis
4.6. Detection of Cytokines in Mouse Colon
4.7. Immunohistochemistry (IHC) and Immune Cytochemistry (ICC)
4.8. Ex Vivo Fibroblast Cultivation
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Donor | Diagnosis | Age/Gender (f/m) | Medication | Montreal Classification | SCCAI/CDAI | Location | Stricturing Complications | Fibrosis | Groups in the NSG Model | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Terminal Ileum | Colon | Ileocolon | Upper GI | Control n (f/m) | Ethanol n (f/m) | ||||||||
UC 1 | UC | 80/f | Infliximab | 5 | 5 (0/5) | 5 (2/3) | |||||||
UC 2 | UC | 54/m | Vedolizumab, Mesalazine | 3 | 4 (2/2) | 6 (0/6); †1 | |||||||
UC 3 | UC | 30/m | Vedolizumab, Glucocorticoids | 7 | 6 (0/6) | 6 (0/6) | |||||||
UC4 | UC | 33/f | Vedolizumab, Glucocorticoids, Mesalazine | 7 | 6 (4/2) | 6 (0/6) | |||||||
UC5 | UC | 34/f | Vedolizumab, Mesalazine | 3 | 6 (0/6) | ||||||||
UC6 | UC | 32/f | Vedolizumab, Mesalazine | 7 | 7 (5/2) | ||||||||
UC7 | UC | 24/m | Infliximab | 12 | 5 (0/5) | ||||||||
Mean | 41 ± 19.55 (3/3) | ||||||||||||
Sum | 21 (6/15) | 41 (7/34) | |||||||||||
CD 1 | CD | 36/m | Vedolizumab | A2/L3/B2 | 0 | yes | no | yes | no | yes | no | 6 (6/0) | 6 (4/2) |
CD 2 | CD | 42/w | None | nd | 0 | 6 (5/1) | |||||||
CD 3 | CD | 26/m | Filgotinib, Glucocorticoids | A2/L3/B1 | 0 | yes | yes | yes | no | no | no | 6 (4/2) | |
CD 4 | CD | 26/w | Vedolizumab, Ustekinumab, Glucocorticoids | A2/L4/B2 | 200 | yes | yes | yes | yes | yes | yes | 6 (2/4) | 6 (4/2) |
CD 5 | CD | 74/m | Glucocorticoids | A2/L3/B2 | 30 | yes | yes | yes | no | yes | yes | 6 (4/2) | |
Mean | 40.8 ± 19.77 (2/3) | ||||||||||||
Sum | 12 (8/4) | 30 (21/9) | |||||||||||
Non-IBD 1 | Non-IBD | 24/w | 4 (0/4) | 4 (4/0) | |||||||||
Non-IBD 2 | Non-IBD | 65/w | 4 (4/0) | 4 (0/4) | |||||||||
Mean | 44 ± 28.28 | ||||||||||||
Sum | 8 (4/4) | 8 (4/4) |
Therapeutic | Target | Outcome | Reference |
---|---|---|---|
Anti-CD1a mab | CD1a | ameliorating | [16] |
Sirolimus | AKT/mTor | ameliorating | [17] |
Pitrakinra | IL-4/IL-13 receptor | deteriorating | [18] |
Copanlisib | PI3K | ameliorating | [19] |
Ritonavir | GLUT | ameliorating | [20] |
DES1 | Kv1.3 | ameliorating | [21] |
Tofacitinib | Jak | ameliorating | [21] |
Infliximab | TNFα | ameliorating | [21] |
Adalimumab | TNFα | ameliorating | [22,23] |
Oxelumab | OX40L | ameliorating | [22] |
Anti-CCR4 mab | CCR4 | deteriorating | [18] |
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Weß, V.; Schuster-Winkelmann, P.; Karatekin, Y.H.; Malik, S.; Beigel, F.; Kühn, F.; Gropp, R. Humanized NSG Mouse Models as a Preclinical Tool for Translational Research in Inflammatory Bowel Diseases. Int. J. Mol. Sci. 2023, 24, 12348. https://doi.org/10.3390/ijms241512348
Weß V, Schuster-Winkelmann P, Karatekin YH, Malik S, Beigel F, Kühn F, Gropp R. Humanized NSG Mouse Models as a Preclinical Tool for Translational Research in Inflammatory Bowel Diseases. International Journal of Molecular Sciences. 2023; 24(15):12348. https://doi.org/10.3390/ijms241512348
Chicago/Turabian StyleWeß, Veronika, Paula Schuster-Winkelmann, Yasemin Hazal Karatekin, Simge Malik, Florian Beigel, Florian Kühn, and Roswitha Gropp. 2023. "Humanized NSG Mouse Models as a Preclinical Tool for Translational Research in Inflammatory Bowel Diseases" International Journal of Molecular Sciences 24, no. 15: 12348. https://doi.org/10.3390/ijms241512348