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Intraocular liver spheroids for non-invasive high-resolution in vivo monitoring of liver cell function

ABSTRACT: Intraocular liver spheroids for non-invasive high-resolution in vivo monitoring of liver cell function

PROVIDER: PRJNA1030415 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26455100.fastq.gz	Fastqsanger.gz
	SRR26455101.fastq.gz	Fastqsanger.gz
	SRR26455102.fastq.gz	Fastqsanger.gz
	SRR26455103.fastq.gz	Fastqsanger.gz
	SRR26455104.fastq.gz	Fastqsanger.gz

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Intraocular liver spheroids for non-invasive high-resolution in vivo monitoring of liver cell function

Project description:Longitudinal monitoring of liver function in vivo is hindered by the lack of high-resolution non-invasive imaging techniques. Using the anterior chamber of the mouse eye as a transplantation site, we have established a platform for longitudinal in vivo imaging of liver spheroids at cellular resolution. Transplanted liver spheroids engraft on the iris, become vascularized and innervated, retain hepatocyte-specific and liver-like features and can be studied by in vivo confocal microscopy. Employing fluorescent probes administered intravenously or spheroids formed from reporter mice, we showcase potential use of this platform exemplified by monitoring hepatocyte cell cycle activity, bile secretion and lipoprotein uptake. Moreover, we show that hepatic lipid accumulation during diet-induced hepatosteatosis is mirrored in intraocular grafts in vivo. The here described technology will provide a crucial tool to study liver physiology and disease progression in both pre-clinical and basic research as well as a drug screening platform in the pharma industry.

2024-01-15 | GSE245944 | GEO

Intraocular liver spheroids for non-invasive high-resolution in vivo monitoring of liver cell function.

Project description:Longitudinal monitoring of liver function in vivo is hindered by the lack of high-resolution non-invasive imaging techniques. Using the anterior chamber of the mouse eye as a transplantation site, we have established a platform for longitudinal in vivo imaging of liver spheroids at cellular resolution. Transplanted liver spheroids engraft on the iris, become vascularized and innervated, retain hepatocyte-specific and liver-like features and can be studied by in vivo confocal microscopy. Employing fluorescent probes administered intravenously or spheroids formed from reporter mice, we showcase the potential use of this platform for monitoring hepatocyte cell cycle activity, bile secretion and lipoprotein uptake. Moreover, we show that hepatic lipid accumulation during diet-induced hepatosteatosis is mirrored in intraocular in vivo grafts. Here, we show a new technology which provides a crucial and unique tool to study liver physiology and disease progression in pre-clinical and basic research.

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Transcriptomic profile of 3D spheroids developed from Astyanax Liver-derived cells - SFL and CFL.

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Project description:The lack of adequate human in vitro models that recapitulate the cellular composition and response of the human liver to injury hampers the development of anti-fibrotic drugs. The goal of this study was to develop a human spheroid culture model to study liver fibrosis by using induced pluripotent stem cell (iPSC)-derived liver cells. iPSCs were independently differentiated towards hepatoblasts (iHepatoblasts), hepatic stellate cells (iHSCs), endothelial cells (iECs) and macrophages (iMΦ), before assembly into free floating spheroids by culturing cells in 96-well U-bottom plates and orbital shaking for up to 21 days to allow further maturation. Through transcriptome analysis, we show further maturation of iECs and iMΦ, the differentiation of the iHepatoblasts towards hepatocyte-like cells (iHeps) and the inactivation of the iHSCs by the end of the 3D culture. Moreover, these cultures display a similar expression of cell-specific marker genes (CYP3A4, PDGFRβ, CD31 and CD68) and sensitivity to hepatoxicity as spheroids made using freshly isolated primary human liver cells. Furthermore, we show the functionality of the iHeps and the iHSCs by mimicking liver fibrosis through iHep-induced iHSC activation, using acetaminophen. In conclusion, we have established a reproducible human iPSC-derived liver culture model that can be used to mimic fibrosis in vitro as a replacement of primary human liver derived 3D models. The model can be used to investigate pathways involved in fibrosis development and to identify new targets for chronic liver disease therapy

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