Cholangiogenic potential of human deciduous pulp stem cell-converted hepatocyte-like cells

Yuniartha, Ratih and Yamaza, Takayoshi and Sonoda, Soichiro and Yoshimaru, Koichiro and Matsuura, Toshiharu and Yamaza, Haruyoshi and Oda, Yoshinao and Ohga, Shouichi and Taguchi, Tomoaki (2021) Cholangiogenic potential of human deciduous pulp stem cell-converted hepatocyte-like cells. Stem Cell Research and Therapy, 12 (1). ISSN 17576512

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Abstract

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. © 2021, The Author(s).

Item Type: Article
Additional Information: Cited by: 11; All Open Access, Gold Open Access, Green Open Access
Uncontrolled Keywords: Animals; Cell Differentiation; Hepatocytes; Humans; Liver Cirrhosis; Mice; Stem Cells; Tooth, Deciduous; albumin; bile salt export pump; carbon tetrachloride; cytokeratin 17; cytokeratin 19; multidrug resistance associated protein 2; multidrug resistance protein 1; paraffin; transcription factor Sox9; tumor necrosis factor; animal experiment; animal model; animal tissue; Article; bile canaliculus; cell differentiation; cell stimulation; cholangiocyte; cholangiogenic potential; controlled study; deciduous tooth; dental pulp stem cell; engraftment; female; graft recipient; hepatobiliary system; hepatocyte like cell; human; human cell; immunohistochemistry; in vivo study; intrahepatic bile duct; liver cell; liver fibrosis; liver injury; mouse; nonhuman; priority journal; protein analysis; protein expression; stem cell transplantation; tissue regeneration; animal; cell differentiation; deciduous tooth; liver cirrhosis; stem cell
Subjects: R Medicine > RB Biomedical Sciences
Divisions: Faculty of Medicine, Public Health and Nursing > Biomedical Sciences
Depositing User: Sri JUNANDI
Date Deposited: 28 Sep 2024 05:33
Last Modified: 28 Sep 2024 05:33
URI: https://ir.lib.ugm.ac.id/id/eprint/4458

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