Evaluation of different media compositions promoting hepatocyte differentiation in the canine liver organoid model

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F24%3A00084815" target="_blank" >RIV/00023001:_____/24:00084815 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S2405844024044517?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2405844024044517?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.heliyon.2024.e28420" target="_blank" >10.1016/j.heliyon.2024.e28420</a>

Result language

angličtina

Original language name

Evaluation of different media compositions promoting hepatocyte differentiation in the canine liver organoid model

Original language description

Organoids are 3 -dimensional (3D) self -assembled structures capable of replicating the microanatomy and physiology of the epithelial components of their organ of origin. Adult stem cell (ASC) derived organoids from the liver have previously been shown to differentiate into primarily mature cholangiocytes, and their partial differentiation into functional hepatocytes can be promoted using specific media compositions. While full morphological differentiation of mature hepatocytes from ASCs has not yet been reported for any species, the functional differentiation can be approximated using various media compositions. Six differentiation media formulations from published studies on hepatic organoids were used for the differentiation protocol. Target species for these protocols were humans, mice, cats, and dogs, and encompassed various combinations and concentrations of four major hepatocyte media components: Bone morphogenetic protein 7 (BMP7), Fibroblast Growth Factor 19 (FGF19), Dexamethasone (Dex), and Gamma-Secretase Inhibitor IX (DAPT). Additionally, removing R-spondin from basic organoid media has previously been shown to drive the differentiation of ASC into mature hepatocytes. Differentiation media (N = 20) were designed to encompass combinations of the four major hepatocyte media components. The preferred differentiation of ASC-derived organoids from liver tissue into mature hepatocytes over cholangiocytes was confirmed by albumin production in the culture supernatant. Out of the twenty media compositions tested, six media resulted in the production of the highest amounts of albumin in the supernatant of the organoids. The cell lines cultured using these six media were further characterized via histological staining, transmission electron microscopy, RNA in situ hybridization, analysis of gene expression patterns, immunofluorescence, and label -free proteomics. The results indicate that preferential hepatocyte maturation from canine ADC -derived organoids from liver tissue is mainly driven by Dexamethasone and DAPT components. FGF19 did not enhance organoid differentiation but improved cell culture survival. Furthermore, we confirm that removing R-spondin from the media is crucial for establishing mature hepatic organoid cultures.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30219 - Gastroenterology and hepatology

Project

—

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Heliyon

ISSN

2405-8440

e-ISSN

2405-8440

Volume of the periodical

10

Issue of the periodical within the volume

7

Country of publishing house

GB - UNITED KINGDOM

Number of pages

18

Pages from-to

"art. no. e28420"

UT code for WoS article

001220973400001

EID of the result in the Scopus database

2-s2.0-85188990846