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Human bile cholangiocyte organoids originate from the extrahepatic bile duct and can repair bile duct scaffolds in vitro

ABSTRACT: Human bile cholangiocyte organoids originate from the extrahepatic bile duct and can repair bile duct scaffolds in vitro

PROVIDER: PRJNA658150 | ENA |

REPOSITORIES: ENA

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Human bile cholangiocyte organoids originate from the extrahepatic bile duct and can repair bile duct scaffolds in vitro

Project description:Cholangiocyte organoids provide a powerful tool for characterizing bile duct epithelium and expanding cholangiocytes for tissue engineering purposes. However, this involves invasively obtained tissue-biopsies via surgery which is not preferential and limits the patient-specific capacities of these cultures. To overcome this, organoid culture were initiated from minimal invasive bile-samples obtained during routine clinical procedures. Characterization revealed that these bile-cholangiocyte organoids originate from the extrahepatic bile duct and are capable to repopulate human extrahepatic bile duct scaffolds. With this, bile duct tissue engineering as well as personalized disease modelling is in sight.

2020-11-19 | GSE156519 | GEO

Comparison of extrahepatic cholangiocyte organoids and freshly isolated common bile duct cholangiocytes

Project description:Despite the impact of bile duct disorders, treatment options remain very limited. Poor access to biliary tissue and restrictions in long-term culture or significant expansion of primary cholangiocytes have posed major challenges for research in the field. These limitations have so far precluded large scale experiments such as transcriptomic and genome-wide analyses which are urgently needed to better understand biliary physiology and pathophysiology. To address this issue, we have developed a novel system for the isolation and propagation of primary cholangiocytes from the extrahepatic bile ducts. The resulting Extrahepatic Cholangiocyte Organoids (ECOs) maintain their genetic stability, transcriptomic profile and function over long term culture and are compatible with regenerative medicine applications such as biliary reconstruction. We established a novel protocol for the isolation and propagation of primary cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs). The aim of this experiment was to provide in depth characterisation of the transcriptome of ECOs during long term culture. We compare the transcriptome of ECOs cultured for 1 passage (P1), 10 passages (P10) and 20 passages (P20) with freshly isolated primary cholangiocytes from the common bile duct. Embryonic Stem Cells (ES) cells are used as a negative control=

2017-07-04 | E-MTAB-4591 | biostudies-arrayexpress

Transcription profiling of undifferentiated human extrahepatic cholangiocyte organoids (ECOs)

Project description:3D cell culture systems (organoids), cultured from extrahepatic bile duct biopsies, resemble biliary epthelium (cholangiocytes) upon culture according to the protocol previously established for culturing intrahepatic cholangiocyte organoids from liver biopsies (Huch et al. Cell 2015). These extrahepatic cholangiocyte organoids (ECOs) in Canonical-Wnt culture conditions maintain their genetic stability, and transcription profile and can be maintained and propagated during long periods of culturing while still maintaining their functional properties. The data presented in this ArrayExpress submission contained micro array results of 3 different ECO lines that were analyzed for their functional cholangiocyte ion-channels, involved in secreting a protective bicarbonate layer. It was shown that these data closely resemble the expression profile of intrahepatic cholangiocyte organoids (ICOs) as described by our group. Results of the ICOs are deposited in the EMBL-EBI ArrayExpress repository under number E-MTAB-9044.

2021-01-01 | E-MTAB-9807 | biostudies-arrayexpress

Comparison of gene expression similarity between mouse extrahepatic bile duct and pancreatic duct epithelia and organoids prepared from these epithelia.

Project description:By RNA sequencing we found that extrahepatic bile duct organoids and pancreatic duct organoids have similar gene expression signatures compared with duct epithelia.

2023-06-06 | GSE196394 | GEO

Distinct Phenotypes of Human Intrahepatic and Extrahepatic Bile duct Organoids and their Applications for Biliary Disease Modeling

Project description:Bile draining by the bile duct system is paramount for good liver function. Diseases which compromise the integrity of the biliary tree are common and often life-threatening. Both intrahepatic and extrahepatic bile ducts contain distinct (stem) cell niches which are important for bile duct homeostasis and repair. A detailed characterization of the cell populations in the extrahepatic bile ducts has been lacking due to the inability of cell culture propagation. The aim of this study was to expand extrahepatic bile duct stem cells using the organoid culture system developed for intrahepatic bile duct cells. Extrahepatic bile duct (eBD)-organoids and intrahepatic (iBD) liver-derived organoids were initiated from paired biopsies of human common bile duct and liver tissue. Organoids of both origins were characterized on the basis of morphology and growth characteristics, gene and protein expression profiles, and their differentiation capacity towards mature cholangiocytes and hepatocytes. Although eBD organoids were very similar to iBD liver organoids, some differences in growth rate, organoid size and gene and protein expression were found. More strikingly, although both organoids could be differentiated towards a mature cholangiocyte phenotype, only iBD organoids can be directed to a mature hepatocyte phenotype. Of note, eBD organoids derived from a cystic fibrosis (CF) patient, harboring the same CFTR mutation (dF508-R1162X) as found in the patient, showed normal Ca2+-dependent Cl- channel and MDR-1 transporter activity but no CFTR channel activity. In conclusion, we here show feasibility of expanding eBD organoids with distinct properties when compared to iBD organoids. These eBD organoids may provide an excellent model for studying bile duct diseases and regenerative medicine.

| EGAS00001003792 | EGA

Human branching cholangiocyte organoids recapitulate embryogenic bile duct development and provide an unique model to study biliary diseases. RNA-Seq

Project description:Although providing promising and unique tools for studying cholangiocytes, current tissue-derived cholangiocyte-organoid systems do not recapitulate the complex architecture of the intrahepatic bile ducts in vitro. Here, we report a new method for creating branching cholangiocyte organoids (BRCO) from human adult tissue to study the intrahepatic biliary tree and diseases. BRCOs self-organize into large complex tubular structures, while closely resembling primary cholangiocytes on a transcriptomic and functional level. They are capable of mimicking branching bile duct development as well as being used for studying diseases in which the biliary tree does not develop properly (Alagille Syndrome). Furthermore, we deliver evidence that our culture method allows for formation of complex cholangiocyte cancer (cholangiocarcinoma, CCA) organoids. These branching CCA organoids resemble the primary tumor more closely compared to previously published protocols as well as showing unique tumor-specific drug responses. In conclusion, our culture method allows for creation of novel (malignant) cholangiocyte-organoids to study the intrahepatic bile ducts.

2022-05-04 | GSE179599 | GEO

Human branching cholangiocyte organoids recapitulate embryogenic bile duct development and provide an unique model to study biliary diseases. scRNA-Seq

2022-05-04 | GSE179597 | GEO

Effect of bile duct ligation on growth factors expression from mouse whole extrahepatic bile duct (EHBD) tissue and cultured mouse neonatal fibroblasts and bile duct organoids

Project description:Effect of bile duct ligation on growth factors expression from mouse whole extrahepatic bile duct (EHBD) tissue and cultured mouse neonatal fibroblasts and bile duct organoids

| PRJNA754373 | ENA

Effect of bile duct ligation on growth factors expression from mouse whole extrahepatic bile duct (EHBD) tissue and cultured mouse neonatal fibroblasts and bile duct organoids

Project description:Dynamic changes in growth factor expression is observed after bile duct ligation at different time points compared to sham-treated mice, corresponding to increase in biliary cell proliferation and repair

2022-05-24 | GSE182049 | GEO

Transcriptional profiling after bile duct ligation identifies PAI-1 as a contributor to cholestatic injury in mice.

Project description:Extrahepatic cholestasis leads to complex injury and repair processes that result in bile infarct formation, neutrophil infiltration, cholangiocyte and hepatocyte proliferation, extracellular matrix remodeling, and fibrosis. To identify early molecular mechanisms of injury and repair after bile duct obstruction, microarray analysis was performed on liver tissue 24 hours after bile duct ligation (BDL) or sham surgery. The most upregulated gene identified encodes plasminogen activator inhibitor 1 (PAI-1, Serpine 1), a protease inhibitor that blocks urokinase plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) activity. Because PAI-1, uPA, and tPA influence growth factor and cytokine processing as well as extracellular matrix remodeling, we evaluated the role of PAI-1 in cholestatic liver injury by comparing the injury and repair processes in wild-type (WT) and PAI-1-deficient (PAI-1-/-) mice after BDL. PAI-1-/- mice had fewer and smaller bile infarcts, less neutrophil infiltration, and higher levels of cholangiocyte and hepatocyte proliferation than WT animals after BDL. Furthermore, PAI-1-/- mice had higher levels of tPA activation and mature hepatocyte growth factor (HGF) after BDL than WT mice, suggesting that PAI-1 effects on HGF activation critically influence cholestatic liver injury. This was further supported by elevated levels of c-Met and Akt phosphorylation in PAI-1-/- mice after BDL. In conclusion, PAI-1 deficiency reduces liver injury after BDL in mice. These data suggest that inhibiting PAI-1 might attenuate liver injury in cholestatic liver diseases.

2011-06-09 | GSE29776 | GEO

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