Dataset Information

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

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.

SUBMITTER: Yuniartha R

PROVIDER: S-EPMC7805240 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Yuniartha Ratih R Yamaza Takayoshi T Sonoda Soichiro S Yoshimaru Koichiro K Matsuura Toshiharu T Yamaza Haruyoshi H Oda Yoshinao Y Ohga Shouichi S Taguchi Tomoaki T

Stem cell research & therapy 20210113 1

<h4>Background</h4>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.<h4>Methods</h4>SHED were induced into SHED-Heps under cytokine stimulation. SHED-Heps were intrasplenically transplanted into chronically CCl<s ...[more]

PMID: 33436050

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Project description:BackgroundTo investigate the therapeutic effect of human dental pulp stem cells (DPSCs) transfected with adenovirus expressing hepatocyte growth factor (HGF) in a mouse model of collagen-induced arthritis (CIA).MethodsDPSCs were modified with Ad-HGF to produce HGF-overexpressing DPSCs, DPSCs-HGF. In experimental mouse CIA model, DPSCs-HGF and DPSCs-Null (modified with Ad-Null) were engrafted via intravenously after disease onset, which was determined by the presence of joint swelling. The therapeutic effects on joints were evaluated at 49 days after collagen injection by histopathological analysis and microcomputed tomography imaging. The inflammatory cytokines were analyzed both in sera and joints via MILLIPLEX kit and immunohistochemical staining, respectively, and the regulatory T cells (Tregs) were analyzed in peripheral blood by using flow cytometry. Furthermore, primary fibroblast-like synoviocytes were isolated, colony formation analysis and FACS were performed to evaluate the effect of HGF on the proliferation and cell cycle of FLSs. Western blot assay was carried out to clarify the signal pathway of HGF-cMet.ResultsWe found that without HGF modification, DPSC transfusion was helpful in controlling autoimmune status, local synovitis, and bone erosion after intravenous administration. However, HGF-modified DPSCs have dual role in rheumatoid arthritis (RA). In the early phase, HGF overexpression inhibited RA progression by its immunosuppressive effects, while in the late phase, HGF promoted synovitis by activating fibroblast-like synoviocytes to produce pathogenic IL-6, accelerating cell proliferation and inducing apoptosis resistance via phosphorylating the c-Met/Akt pathway. The overall effect of HGF modification attenuated the therapeutic effect of DPSCs.ConclusionsOur study provides a comprehensive evaluation of the therapeutic effect of DPSCs in the mouse model and a primary answer to the divergence of whether HGF is harmful or helpful in RA.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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