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Domino hepatocyte transplantation using explanted human livers with metabolic defects attenuates D-GalN/LPS-induced acute liver failure.
- Source :
-
Journal of Translational Medicine . 10/20/2022, Vol. 20 Issue 1, p1-12. 12p. - Publication Year :
- 2022
-
Abstract
- <bold>Background: </bold>Explanted livers from patients with inherited metabolic liver diseases possess the potential to be a cell source of good-quality hepatocytes for hepatocyte transplantation (HT). This study evaluated the therapeutic effects of domino HT using hepatocytes isolated from explanted human livers for acute liver failure (ALF).<bold>Methods: </bold>Isolated hepatocytes were evaluated for viability and function and then transplanted into D-galactosamine/lipopolysaccharide-induced ALF mice via splenic injection. The survival rate was analyzed by the Kaplan-Meier method and log-rank test. Liver function was evaluated by serum biochemical parameters, and inflammatory cytokine levels were measured by ELISA. The pathological changes in the liver tissues were assessed by hematoxylin-eosin staining. Hepatocyte apoptosis was investigated by TUNEL, and hepatocyte apoptosis-related proteins were detected by western blot. The localization of human hepatocytes in the injured mouse livers was detected by immunohistochemical analyses.<bold>Results: </bold>Hepatocytes were successfully isolated from explanted livers of 10 pediatric patients with various liver-based metabolic disorders, with an average viability of 85.3% ± 13.0% and average yield of 9.2 × 106 ± 3.4 × 106 cells/g. Isolated hepatocytes had an excellent ability to secret albumin, produce urea, uptake indocyanine green, storage glycogen, and express alpha 1 antitrypsin, albumin, cytokeratin 18, and CYP3A4. Domino HT significantly reduced mortality, decreased serum levels of alanine aminotransferase and aspartate aminotransferase, and improved the pathological damage. Moreover, transplanted hepatocytes inhibited interleukin-6 and tumor necrosis factor-α levels. Domino HT also ameliorates hepatocyte apoptosis, as evidenced by decreased TUNEL positive cells. Positive staining for human albumin suggested the localization of human hepatocytes in ALF mice livers.<bold>Conclusion: </bold>Explanted livers from patients with inheritable metabolic disorders can serve as a viable cell source for cell-based therapies. Domino HT using hepatocytes with certain metabolic defects has the potential to be a novel therapeutic strategy for ALF. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ALPHA 1-antitrypsin
*LIVER failure
*LIVER
*KERATIN
*ASPARTATE aminotransferase
*LIVER cells
*PROTEINS
*LIPOPOLYSACCHARIDES
*INTERLEUKINS
*ALBUMINS
*UREA
*INDOLE compounds
*METABOLIC disorders
*BENZOPYRANS
*CARBOHYDRATES
*TUMOR necrosis factors
*RESEARCH funding
*GLYCOGEN
*OXIDOREDUCTASES
*FLUORESCENT dyes
*ACUTE diseases
*ANIMALS
*MICE
*ALANINE aminotransferase
Subjects
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 20
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 159792273
- Full Text :
- https://doi.org/10.1186/s12967-022-03674-3