Immunogenicity of autologous and allogeneic human primary cholangiocyte organoids
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1066756 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27663700_1.fastq.gz | Fastqsanger.gz | |||
| SRR27663700_2.fastq.gz | Fastqsanger.gz | |||
| SRR27663800_1.fastq.gz | Fastqsanger.gz | |||
| SRR27663800_2.fastq.gz | Fastqsanger.gz | |||
| SRR27663701_1.fastq.gz | Fastqsanger.gz |
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Project description:Primary human cells cultured in 3D organoid format have great promise as potential regenerative cellular therapies, but their immunogenicity has not yet been fully characterized. In this study, we use in vitro co-cultures and in vivo humanized mouse experimental models to examine the human immune response to autologous and allogeneic primary cholangiocyte organoids (PCOs). Our data demonstrate that PCOs upregulate the expression of HLA-I and HLA-II in inflammatory conditions. The immune response to allogeneic PCOs is driven by both HLA-I and HLA-II and is substantially ameliorated by donor-recipient HLA matching. Autologous PCOs induce a low-level immune infiltration into the graft site, while allogeneic cells display evolving stages of immune rejection in vivo. Our findings have important implications for the design and clinical translation of autologous and allogeneic organoid cellular therapies.
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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.
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Project description:3D cell culture systems (organoids), cultured from liver biopsies, resemble biliary epthelium (cholangiocytes) upon culture. These intrahepatic cholangiocyte organoids (ICOs) maintain their gentic stability, transcription profile and can be maintained propagated during long periods of culturing while still maintaining their functional properties. The data presented in this ArrayExpress submission contained micro array results of 6 from 15 different ICO 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 profiles of extrahepatic cholangiocyte organoids (ECOs), previously described by Sampaziotis et al. and deposited in the EMBL-EBI ArrayExpress repository (E-MTAB-4591)
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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.
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