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Long-term maintenance of functional primary human hepatocytes using small molecules

ABSTRACT: Long-term maintenance of functional primary human hepatocytes using small molecules

PROVIDER: PRJNA557132 | ENA |

REPOSITORIES: ENA

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Long-term maintenance of functional primary human hepatocytes using small molecules

Project description:Primary human hepatocytes (PHHs) were cultured with or without a cocktail of four small molecules, Y-27632, PD0325901, A83-01 and CHIR99021 (termed YPAC), and their transcriptomes after a long-trm culture were compared.

2019-09-01 | GSE135011 | GEO

Long-term Functional Maintenance of Primary Human Hepatocytes In Vitro

Project description:Functional maintenance of terminally differentiated cells outside the in vivo microenvironment has proved challenging. Current strategies that manipulate cell-cell or cell-matrix connections are difficult to constitute complex regulatory networks for cell function maintenance. Small molecules are easily combined for flexible spatiotemporal modulations, theoretically favorable for synergetic regulation of cell-innate signaling pathways to maintain cell function in vitro. Here, we developed small-molecule cocktails enabling robust maintenance of primary human hepatocytes (PHHs) longer than four weeks, with gene expression profiles, resembling those of freshly isolated PHHs; and prolong-cultured PHHs, for the first time, could maintain drug-metabolizing activities of enzymes accounting for over 80% of drug-oxidation and support hepatitis B virus infection in vitro for over one month. Our study demonstrates that this chemical approach effectively maintains terminally differentiated hepatocytes in vitro, which could be extended to various cell types.

2019-04-26 | GSE108198 | GEO

Long-term Functional Maintenance of Primary Human Hepatocytes In Vitro

Project description:Long-term Functional Maintenance of Primary Human Hepatocytes In Vitro

| PRJNA423006 | ENA

Global transcriptional analysis of human functional hepatocytes Long-term maintained by small-molecule cocktails by RNA-seq

Project description:Functional maintenance of terminally differentiated cells outside the in vivo microenvironment has proved challenging. Current strategies that manipulate cell-cell or cell-matrix connections are difficult to constitute complex regulatory networks for cell function maintenance. Small molecules are easily combined for flexible spatiotemporal modulations, theoretically favorable for synergetic regulation of cell-innate signaling pathways to maintain cell function in vitro. Here, we developed small-molecule cocktails enabling robust maintenance of primary human hepatocytes (PHHs) longer than four weeks, with gene expression profiles, resembling those of freshly isolated PHHs; and prolong-cultured PHHs, for the first time, could maintain drug-metabolizing activities of enzymes accounting for over 80% of drug-oxidation and support hepatitis B virus infection in vitro for over one month. Importantly, this cocktail also promotes functional maturation of human pluripotent stem cell-derived hepatocytes. Our study demonstrates that this chemical approach effectively maintains terminally differentiated hepatocytes in vitro, which could be extended to various cell types.

2019-04-26 | GSE120226 | GEO

Long-term maintenance of functional primary human hepatocytes in 3D gelatin matrices produced by solution blow spinning.

Project description: Not available

| S-EPMC8505433 | biostudies-literature

Single cell RNA seq of long-term 3D culture of mouse primary hepatocytes induced by TNFa

Project description:Single cell RNA seq to compare the gene expression profile of hepatocytes cultured in expansion or differentiation media to primary hepatocytes

2019-02-01 | GSE120067 | GEO

RNA-seq transcriptional profiling in primary human hepatocytes, short- and long-term cultured Proliferating human hepatocytes (in vitro/in vivo)

Project description:One of the major challenges of cell therapy is manufacturing of the effective seed cells, which inevitably requires the expansion of cells in vitro. Although considerable progresses have been achieved in expansion of primary human hepatocytes (PHH) in vitro, the transplantation efficiency of proliferating human hepatocytes was decreased with the extended culture. The mechanism of declined transplantation is not clear.Here, we found that long-term cultured proliferating human hepatocytes (lc-ProliHH) significantly upregulated chemokines and proinflammatory cytokines associated with innate immune response. Moreover, lc-ProliHH elicited robust recruitment of macrophages and neutrophils at early stage of transplantation, and being cleared by macrophages caused the engraftment efficiency reduction.Based on these findings, we designed to treat recipient with Dexamethasone (Dex), which decreased the response of innate immune cells and significantly increased the transplantation efficiency to a level approximate to PHH in the liver-injured mice. Furthermore, ProliHH organoid reduced the expression of cytokine genes and behaved close to mature hepatocyte, and as a result, ameliorated their transplantation efficiency as well.

2024-01-25 | GSE184448 | GEO

Long-Term Cell Fate and Functional Maintenance of Human Hepatocyte through Stepwise Culture Configuration

Project description:Humanized Liver Chimeric Mice (HLCM)-derived human hepatocytes (HLCM-HH) were maintained in the absence (non-treatment; NT) or presence of either 2% DMSO or DMSO2 (140mM)-containing medium for 7 days. HepG2 cells and Huh7 cells were cultured with 2% DMSO containing medium for 7 days. Then total cellular RNA was extracted for the subsequent poly-A based mRNA sequencing analysis.

2023-01-12 | GSE207912 | GEO

miR1908-5p primary hepatocytes

Project description:miR1908-5p primary hepatocytes

| PRJNA745934 | ENA

Phosphoproteomics analysis reveals changes in primary hepatocytes following Wdr6 knockout

Project description:WDR6 was a scaffolding/ regulatory protein that interacts with diverse signaling molecules. Our findings showed that WDR6 might be involved in post-translational modifications (PTMs). Then we performed transcriptomic analysis of primary hepatocytes from WDR6-WKO and control mice.

2023-09-22 | PXD034542 | Pride

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