Cholangiogenic potential of human deciduous pulp stem cell-converted hepatocyte-like cells
| Autor: | Shouichi Ohga, Koichiro Yoshimaru, Tomoaki Taguchi, Takayoshi Yamaza, Yoshinao Oda, Toshiharu Matsuura, Haruyoshi Yamaza, Soichiro Sonoda, Ratih Yuniartha |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Liver Cirrhosis
Pathology medicine.medical_specialty Medicine (miscellaneous) Intrahepatic bile ducts Biochemistry Genetics and Molecular Biology (miscellaneous) Human deciduous pulp stem cell-converted hepatocyte-like cells Cholangiocyte lcsh:Biochemistry Mice medicine Animals Humans lcsh:QD415-436 Tooth Deciduous ABCB11 Intrahepatic bile duct regeneration lcsh:R5-920 Chemistry Tumor necrosis factor alpha Research Stem Cells Regeneration (biology) Cell Differentiation Cell Biology Multidrug Resistance-Associated Protein 2 Interlobular bile ducts Transplantation medicine.anatomical_structure Hepatocyte Hepatocytes Molecular Medicine Chronic liver fibrosis Stem cell lcsh:Medicine (General) |
| Zdroj: | Stem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-13 (2021) Stem Cell Research & Therapy |
| ISSN: | 1757-6512 |
| Popis: | Background Stem cells from human exfoliated deciduous teeth (SHED) have been reported to show the in vivo and in vitro hepatic differentiation, SHED-Heps; however, the cholangiogenic potency of SHED-Heps remains unclear. Here, we hypothesized that SHED-Heps contribute to the regeneration of intrahepatic bile duct system in chronic fibrotic liver. Methods SHED were induced into SHED-Heps under cytokine stimulation. SHED-Heps were intrasplenically transplanted into chronically CCl4-treated liver fibrosis model mice, followed by the analysis of donor integration and hepatobiliary metabolism in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile duct system in the recipient liver. Furthermore, SHED-Heps were induced under the stimulation of tumor necrosis factor alpha (TNFA). Results The intrasplenic transplantation of SHED-Heps into CCl4-treated mice showed that donor SHED-Heps behaved as human hepatocyte paraffin 1- and human albumin-expressing hepatocyte-like cells in situ and ameliorated CCl4-induced liver fibrosis. Of interest, the integrated SHED-Heps not only expressed biliary canaliculi ATP-binding cassette transporters including ABCB1, ABCB11, and ABCC2, but also recruited human keratin 19- (KRT19-) and KRT17-positive cells, which are considered donor-derived cholangiocytes, regenerating the intrahepatic bile duct system in the recipient liver. Furthermore, the stimulation of TNFA induced SHED-Heps into KRT7- and SRY-box 9-positive cells. Conclusions Collectively, our findings demonstrate that infused SHED-Heps showed cholangiogenic ability under the stimulation of TNFA in CCl4-damaged livers, resulting in the regeneration of biliary canaliculi and interlobular bile ducts in chronic fibrotic liver. Thus, the present findings suggest that SHED-Heps may be a novel source for the treatment of cholangiopathy. |
| Databáze: | OpenAIRE |
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