Multi-Organ Morphological Findings in a Humanized Murine Model of Sickle Cell Trait
Abstract
:1. Introduction
2. Results
2.1. Hematological Values
2.2. Erythropoiesis, Spleen Size, and Organ Iron Content
2.3. Histopathology
2.3.1. Liver
2.3.2. Spleen
2.3.3. Lung
2.3.4. Kidney
2.3.5. Heart
2.4. Transmission Electron Microscopy
2.4.1. Liver
2.4.2. Spleen
2.4.3. Lung
2.4.4. Kidney
2.4.5. Heart
3. Discussion
4. Materials and Methods
4.1. Animal Model
4.1.1. Hematological Values
4.1.2. Flow Cytometry
4.1.3. Spleen Size and Organ Iron Content
4.2. Histopathology
- -
- normal/minimal damage when the fields involved were from 0 to 30%
- -
- mild/moderate damage when the fields involved were from 30 to 70%
- -
- severe damage when the fields involved were from 70 to 100%
4.3. Transmission Electron Microscopy
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mice | RBC (M/mm3) | Hb (g/dL) | Hct (%) | MCV (fl) | MCH (pg) | MCHC (g/dL) | RDW |
---|---|---|---|---|---|---|---|
HBBA/A | 9.7 ± 0.3 | 12.8 ± 1.3 | 32.2 ± 1.7 | 33.2 ± 1.7 | 13.0 ± 0.3 | 39.9 ± 2.2 | 17.5 ± 2.8 |
HBBA/S | 9.6 ± 0.6 ### | 11.7 ± 0.5 ### | 31.1 ± 1.0 | 32.5 ± 2.0 ## | 12.2 ± 0.5 * | 37.7 ± 1.0 # | 17.6 ± 2.3 # |
HBBS/S | 6.2 ± 1.5 | 8.5 ± 0.8 | 26.3 ± 7.3 | 42.4 ± 4.6 | 15.2 ± 2.3 | 33.3 ± 5.0 | 20.6 ± 2.2 |
Mean (DS): | |||||
---|---|---|---|---|---|
Ter119+ CD71+/Ter119+ CD71− % | |||||
Mice | BM Cells | Spleen Index | Iron Liver, μg | Iron Spleen, μg | Iron Heart, μg |
HBBA/A | 1.97 ± 0.53 | 895 ± 272 | 122.57± 70.4 | 95.8 ± 55.6 | 9.3 ± 4.6 |
HBBA/S | 2.68 ± 0.92 ## | 1245.7 ± 203.6 ### | 106.9 ± 30.8 ### | 94.2 ± 28.4 ## | 8.6 ± 4.4 |
HBBS/S | 6.67 ± 2.03 | 6414 ± 684 | 896.4 ± 112.65 | 1409.76 ± 378.1 | 19.45 ± 8.4 |
Liver | Spleen | Lung | Kidney | Heart | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Grade | n | n | n | n | n | |||||
Normal/ Minimal | minimal cell stress, preserved tissue architecture | 2 | minimal increase in the white pulp | 0 | absent to low inflammation, minimal capillary congestion | 5 | mononuclear infiltrates, swelling of tubular cells, vascular congestion | 0 | normally stained fibers, clearly visible nuclei, normal vessels, no connective fiber deposits, focal weaving | 5 |
Mild/ moderate | mild ischemic lesion, hepatocyte vacuolization, light mononuclear infiltrates, pericentral vein tissue pallor | 3 | increase in white pulp, vascular ectasia | 5 | mononuclear infiltrates, capillary congestion, edema, dilated capillaries, thickness of intima and media of pulmonary vessels | 0 | mononuclear infiltrates, steatosis and swelling of tubular cells, vascular congestion | 5 | pale staining of myocardiocytes, ischemic swelling, disorganization of histoarchitecture | 0 |
Severe | large areas of necrosis, infarcts, mononuclear infiltrates, endovascular sickle cells | 0 | gross infarcts, increased spleen diameter, pigment deposits | 0 | infarcts, emphysema, hemorrhage, edema, thickness of intima and media of pulmonary vessels | 0 | gross infarcts, glomerular necrosis, papillary necrosis | 0 | Fragmentation and pale staining of myocardiocytes, nuclei not clearly visible, large areas of coagulative necrosis | 0 |
Genotype | Sex | |
---|---|---|
Control 1 (C1) | HBBA/A | Male |
Control 2 (C2) | HBBA/A | Male |
Mouse 1 (M1) | HBBA/S | Male |
Mouse 2 (M2) | HBBA/S | Male |
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Trucas, M.; Burattini, S.; Porcu, S.; Simbula, M.; Ristaldi, M.S.; Kowalik, M.A.; Serra, M.P.; Gobbi, P.; Battistelli, M.; Perra, A.; et al. Multi-Organ Morphological Findings in a Humanized Murine Model of Sickle Cell Trait. Int. J. Mol. Sci. 2023, 24, 10452. https://doi.org/10.3390/ijms241310452
Trucas M, Burattini S, Porcu S, Simbula M, Ristaldi MS, Kowalik MA, Serra MP, Gobbi P, Battistelli M, Perra A, et al. Multi-Organ Morphological Findings in a Humanized Murine Model of Sickle Cell Trait. International Journal of Molecular Sciences. 2023; 24(13):10452. https://doi.org/10.3390/ijms241310452
Chicago/Turabian StyleTrucas, Marcello, Sabrina Burattini, Susanna Porcu, Michela Simbula, Maria Serafina Ristaldi, Marta Anna Kowalik, Maria Pina Serra, Pietro Gobbi, Michela Battistelli, Andrea Perra, and et al. 2023. "Multi-Organ Morphological Findings in a Humanized Murine Model of Sickle Cell Trait" International Journal of Molecular Sciences 24, no. 13: 10452. https://doi.org/10.3390/ijms241310452