Stem cell research & therapy · 2021
Cholangiogenic potential of human deciduous pulp stem cell-converted hepatocyte-like cells.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yuniartha Ratih, Yamaza Takayoshi, Sonoda Soichiro, Yoshimaru Koichiro, Matsuura Toshiharu, Yamaza Haruyoshi, Oda Yoshinao, Ohga Shouichi, Taguchi Tomoaki
Аннотация
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.
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.