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Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency
BACKGROUND: Biliary atresia (BA) is a severe hepatobiliary disease in infants that ultimately results in hepatic failure; however, its pathological mechanism is poorly elucidated. Current surgical options, including Kasai hepatoportoenterostomy and orthotopic liver organ transplantations, are pallia...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607730/ https://www.ncbi.nlm.nih.gov/pubmed/34809720 http://dx.doi.org/10.1186/s13287-021-02652-8 |
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author | Sonoda, Soichiro Yoshimaru, Koichiro Yamaza, Haruyoshi Yuniartha, Ratih Matsuura, Toshiharu Yamauchi-Tomoda, Erika Murata, Sara Nishida, Kento Oda, Yoshinao Ohga, Shouichi Tajiri, Tasturo Taguchi, Tomoaki Yamaza, Takayoshi |
author_facet | Sonoda, Soichiro Yoshimaru, Koichiro Yamaza, Haruyoshi Yuniartha, Ratih Matsuura, Toshiharu Yamauchi-Tomoda, Erika Murata, Sara Nishida, Kento Oda, Yoshinao Ohga, Shouichi Tajiri, Tasturo Taguchi, Tomoaki Yamaza, Takayoshi |
author_sort | Sonoda, Soichiro |
collection | PubMed |
description | BACKGROUND: Biliary atresia (BA) is a severe hepatobiliary disease in infants that ultimately results in hepatic failure; however, its pathological mechanism is poorly elucidated. Current surgical options, including Kasai hepatoportoenterostomy and orthotopic liver organ transplantations, are palliative; thus, innovation in BA therapy is urgent. METHODS: To examine whether BA-specific post-natal stem cells are feasible for autologous cell source for BA treatment, we isolated from human exfoliated deciduous teeth, namely BA-SHED, using a standard colony-forming unit fibroblast (CFU-F) method and compared characteristics as mesenchymal stem cells (MSCs) to healthy donor-derived control SHED, Cont-SHED. BA-SHED and Cont-SHED were intrasplenically transplanted into chronic carbon tetrachloride (CCl(4))-induced liver fibrosis model mice, followed by the analysis of bile drainage function and donor integration in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile ducts in the recipient’s liver using anti-human specific keratin 19 (KRT19) antibody. RESULTS: BA-SHED formed CFU-F, expressed MSC surface markers, and exhibited in vitro mesenchymal multipotency similar to Cont-SHED. BA-SHED showed less in vitro hepatogenic potency than Cont-SHED. Cont-SHED represented in vivo bile drainage function and KRT19-positive biliary regeneration in chronic carbon tetrachloride-induced liver fibrosis model mice. BA-SHED failed to show in vivo biliary potency and bile drainage function compared to Cont-SHED. CONCLUSION: These findings indicate that BA-SHED are not feasible source for BA treatment, because BA-SHED may epigenetically modify the underlying prenatal and perinatal BA environments. In conclusion, these findings suggest that BA-SHED-based studies may provide a platform for understanding the underlying molecular mechanisms of BA development and innovative novel modalities in BA research and treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02652-8. |
format | Online Article Text |
id | pubmed-8607730 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86077302021-11-22 Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency Sonoda, Soichiro Yoshimaru, Koichiro Yamaza, Haruyoshi Yuniartha, Ratih Matsuura, Toshiharu Yamauchi-Tomoda, Erika Murata, Sara Nishida, Kento Oda, Yoshinao Ohga, Shouichi Tajiri, Tasturo Taguchi, Tomoaki Yamaza, Takayoshi Stem Cell Res Ther Research BACKGROUND: Biliary atresia (BA) is a severe hepatobiliary disease in infants that ultimately results in hepatic failure; however, its pathological mechanism is poorly elucidated. Current surgical options, including Kasai hepatoportoenterostomy and orthotopic liver organ transplantations, are palliative; thus, innovation in BA therapy is urgent. METHODS: To examine whether BA-specific post-natal stem cells are feasible for autologous cell source for BA treatment, we isolated from human exfoliated deciduous teeth, namely BA-SHED, using a standard colony-forming unit fibroblast (CFU-F) method and compared characteristics as mesenchymal stem cells (MSCs) to healthy donor-derived control SHED, Cont-SHED. BA-SHED and Cont-SHED were intrasplenically transplanted into chronic carbon tetrachloride (CCl(4))-induced liver fibrosis model mice, followed by the analysis of bile drainage function and donor integration in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile ducts in the recipient’s liver using anti-human specific keratin 19 (KRT19) antibody. RESULTS: BA-SHED formed CFU-F, expressed MSC surface markers, and exhibited in vitro mesenchymal multipotency similar to Cont-SHED. BA-SHED showed less in vitro hepatogenic potency than Cont-SHED. Cont-SHED represented in vivo bile drainage function and KRT19-positive biliary regeneration in chronic carbon tetrachloride-induced liver fibrosis model mice. BA-SHED failed to show in vivo biliary potency and bile drainage function compared to Cont-SHED. CONCLUSION: These findings indicate that BA-SHED are not feasible source for BA treatment, because BA-SHED may epigenetically modify the underlying prenatal and perinatal BA environments. In conclusion, these findings suggest that BA-SHED-based studies may provide a platform for understanding the underlying molecular mechanisms of BA development and innovative novel modalities in BA research and treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02652-8. BioMed Central 2021-11-22 /pmc/articles/PMC8607730/ /pubmed/34809720 http://dx.doi.org/10.1186/s13287-021-02652-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Sonoda, Soichiro Yoshimaru, Koichiro Yamaza, Haruyoshi Yuniartha, Ratih Matsuura, Toshiharu Yamauchi-Tomoda, Erika Murata, Sara Nishida, Kento Oda, Yoshinao Ohga, Shouichi Tajiri, Tasturo Taguchi, Tomoaki Yamaza, Takayoshi Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency |
title | Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency |
title_full | Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency |
title_fullStr | Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency |
title_full_unstemmed | Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency |
title_short | Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency |
title_sort | biliary atresia-specific deciduous pulp stem cells feature biliary deficiency |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607730/ https://www.ncbi.nlm.nih.gov/pubmed/34809720 http://dx.doi.org/10.1186/s13287-021-02652-8 |
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