Comparison of the Efficacy of Two Routes of Administration of Human Amniotic Epithelial Cells in Cell Therapy of Acute Hepatic Insufficiency
Abstract
:1. Introduction
2. Results
2.1. Characteristics of Isolated hAECs
2.2. Assessment of the Degree of Liver Damage
2.2.1. Assessment of Biochemical Parameters of Collected Blood
2.2.2. Evaluation of Histopathological Changes in the Liver
2.2.3. Assessment of Liver Cell Proliferation and Apoptosis
2.3. Identification of Transplanted Human Amniotic Cells in the Organs of Recipient Mice
3. Discussion
4. Materials and Methods
4.1. Experimental Model of Hepatotoxicity
4.2. Isolation of hAECs
4.3. Assessment of Viability and Phenotype of Isolated Amniotic Cells
4.4. Delivery of Isolated hAECs
4.5. Evaluation of the Liver Damage
4.5.1. Blood Parameters in the Recipient Mice
4.5.2. Histopathological Evaluation
4.5.3. Assessment of Liver Damage Based on Histological Staining with Haematoxylin and Eosin
4.5.4. Evaluation of Proliferative and Apoptotic Activity of Hepatic Cells
4.6. Identification of Transplanted Human Amniotic Cells in Recipient Mouse Tissues
4.6.1. Immunohistochemical Detection of hAECs
4.6.2. Identification of Human DNA from Transplanted hAECs
4.7. Statistical Analysis
5. Conclusions
- The biodistribution of transplanted hAECs varies depending on the route of administration and the degree of liver damage.
- After intravenous administration, most of the cells engraft in the lungs, while after intraperitoneal administration, they engraft primarily in the liver in both intoxicated and native mice.
- The increased presence of hAECs in the spleen is associated with progressive liver toxicity regardless of the route of administration—the greater the liver damage, the greater the number of hAECs in the spleen.
- After intravenous administration, a large number of the grafted hAECs in the lungs can have a therapeutic effect on the damaged liver.
- The therapeutic effect of intraperitoneally administered hAECs on histopathological and regenerative changes in the liver is very limited due to the low efficiency of cell engraftment in the damaged organ.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Intoxication/Cell Delivery | Time after Injection | Route of hAEC Administration | ALAT | ASAT | ALP | TP | Glucose |
---|---|---|---|---|---|---|---|
D-GaIN | 6 h | intraperitoneally | 9% ↑ | 18% ↑ | 58% a↑ | 18% a↓ | 89% a↓ |
24 h | 81% a↑ | 81% a↑ | 56% a↑ | 1% ↓ | 329% a↓ | ||
72 h | 76% a↑ | 46% a↑ | 41% a↑ | 7% ↓ | 170% a↓ | ||
hAEC | 3 h | intraperitoneally | 37% ↑ | 8% ↑ | 59% a↑ | 0% | 51% a↓ |
intravenously | 61% a↑ | 82% a↑ | 52% ↑ | 2% ↓ | 32% ↓ | ||
21 h | intraperitoneally | 9% ↑ | 12% ↑ | 63% a↑ | 2% ↓ | 24% a↓ | |
intravenously | 56%↑ | 55% a↑ | 49% a↑ | 3% ↓ | 37% ↓ | ||
69 h | intraperitoneally | 6% ↑ | 13% ↓ | 62% a↑ | 7% ↑ | 85% a↓ | |
intravenously | 11%↓ | 38% ↑ | 21% ↑ | 3% ↑ | 41% ↓ | ||
hAEC + D-GaIN | 3/6 h | intraperitoneally | 27% ↑ | 6% ↑ | 7% ↑ | 10% b↑ | 0% |
intravenously | 20% ↑ | 39% ↑ | 13% ↓ | 9% ↑ | 38% ↓ | ||
21/24 h | intraperitoneally | 41% ↑ | 16% ↑ | 6% ↓ | 7% ↓ | 6% ↓ | |
intravenously | 31% ↓ | 29% ↑ | 3% ↓ | 0% | 34% ↑ | ||
69/72 h | intraperitoneally | 65% ↑ | 40% ↑ | 15% ↑ | 6% ↑ | 11% ↑ | |
intravenously | 443% b↓ | 89% ↓ | 38% ↓ | 15% b↑ | 36% b↑ |
Organ | Route of hAEC Administration | Untreated Mouse | Treated Mouse | ||||
---|---|---|---|---|---|---|---|
Time [h] | |||||||
3 | 21 | 69 | 3 | 21 | 69 | ||
Lung | Intraperitoneally | 2 | 0 b | 5 b,d | 0 | 0 | 0 |
Intravenously | 138,397 a | 23,581 a,b | 19,400 a,b | 23,496 a | 77,361 a | 11,450 a | |
Spleen | Intraperitoneally | 332 | 0 b | 92 | 69 | 788 c,d | 361 c,f |
Intravenously | 0 | 5 | 0 | 0 | 71 a | 55 a | |
Liver | Intraperitoneally | 449 | 125 | 343 | 261 | 139 | 552 e |
Intravenously | 189 | 0 b | 59 a | 22 a | 0 a | 0 a | |
Blood | Intraperitoneally | 0 | 11 b | 8 b | 22 | 33 | 0 |
Intravenously | 18 a | 0 | 0 | 905 a | 0 a,c | 0 |
Group | Subgroups | Route of Administration | Injection | |
---|---|---|---|---|
Control group | I | 72O | Intraperitoneally | NaCl |
II | 72Z | Intravenously | ||
hAEC injection group | III | 3O | Intraperitoneally | hAEC |
21O | ||||
69O | ||||
IV | 3Z | Intravenously | ||
21Z | ||||
69Z | ||||
D-GaIN injection group | 6G | Intraperitoneally | D-GaIN | |
V | 24G | |||
72G | ||||
D-GaIN and hAEC injection group | VI | 6GO | D-GaIN intraperitoneally; hAEC intraperitoneally | D-GaIN and hAEC after 3 h |
24GO | ||||
72GO | ||||
VII | 6GZ | D-GaIN intraperitoneally; hAEC intravenously | ||
24GZ | ||||
72GZ |
Scale | Hepatitis Exponents | Scale | Exponents of Liver Parenchymal Injury | Scale | Presence of Acidophilic Apoptotic Bodies |
---|---|---|---|---|---|
1 | No or minimal inflammation; absent or single infiltration in zone 1 of the hepatic stroma; or single infiltration of the parenchyma | 1 | No foci of damage/single foci of damage; parenchymal oedema | 1 | None |
2 | Infiltration in zone 1 of the hepatic stroma occupying <50% of the examined area | 2 | At least one outbreak of damage | 2 | Singular |
3 | Infiltration in zone 1 of the hepatic stroma occupying >50% of the examined area | 3 | Multiple foci of damage; necrosis; disruption of parenchymal architecture | 3 | Multiple |
Scale | Evaluation |
---|---|
1 | No protein expression |
2 | Protein present in <10 cells examined |
3 | Protein present in 10–25 cells tested |
4 | Protein present in 26–50 cells tested |
5 | Protein present in >50 cells tested |
Gene | Name | Sequence | Product Length | Tm [°C] |
---|---|---|---|---|
CB | Cytochrome b | F: 5′-CCCATACATTGGGACAGACC-3′ R: 5′-GACGGATCGGAGAATTGTGT-3′ | 394 | 82.5 |
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Wieczorek, P.; Czekaj, P.; Król, M.; Bogunia, E.; Hermyt, M.; Kolanko, E.; Toczek, J.; Skubis-Sikora, A.; Grajoszek, A.; Stojko, R. Comparison of the Efficacy of Two Routes of Administration of Human Amniotic Epithelial Cells in Cell Therapy of Acute Hepatic Insufficiency. Pharmaceuticals 2024, 17, 476. https://doi.org/10.3390/ph17040476
Wieczorek P, Czekaj P, Król M, Bogunia E, Hermyt M, Kolanko E, Toczek J, Skubis-Sikora A, Grajoszek A, Stojko R. Comparison of the Efficacy of Two Routes of Administration of Human Amniotic Epithelial Cells in Cell Therapy of Acute Hepatic Insufficiency. Pharmaceuticals. 2024; 17(4):476. https://doi.org/10.3390/ph17040476
Chicago/Turabian StyleWieczorek, Patrycja, Piotr Czekaj, Mateusz Król, Edyta Bogunia, Mateusz Hermyt, Emanuel Kolanko, Jakub Toczek, Aleksandra Skubis-Sikora, Aniela Grajoszek, and Rafał Stojko. 2024. "Comparison of the Efficacy of Two Routes of Administration of Human Amniotic Epithelial Cells in Cell Therapy of Acute Hepatic Insufficiency" Pharmaceuticals 17, no. 4: 476. https://doi.org/10.3390/ph17040476