2022
DOI: 10.1016/j.biomaterials.2022.121575
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Development of human pluripotent stem cell-derived hepatic organoids as an alternative model for drug safety assessment

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Cited by 36 publications
(43 citation statements)
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“… 191 The applicability of hepatic organoids derived from human iPSCs for drug toxicity assessment was demonstrated by comprehensive functional analysis of CYP450-mediated drug metabolism. 339 These cases demonstrate the versatility of organoids and their consistency with in vivo therapy, and these validation results promote the ubiquitous role of organoids in drug selection and prediction for clinical treatment.…”
Section: Digestive System Organoid Models and Precision And Personali...mentioning
confidence: 72%
“… 191 The applicability of hepatic organoids derived from human iPSCs for drug toxicity assessment was demonstrated by comprehensive functional analysis of CYP450-mediated drug metabolism. 339 These cases demonstrate the versatility of organoids and their consistency with in vivo therapy, and these validation results promote the ubiquitous role of organoids in drug selection and prediction for clinical treatment.…”
Section: Digestive System Organoid Models and Precision And Personali...mentioning
confidence: 72%
“…However, the use of matrigel is a crucial impairment for its translation, since matrigel is a poorly defined animal-derived matrix causing animal protein contamination and reproducibility (lot variation) issues. Researchers are now working on development of alternative biomaterial, mainly to replace matrigel with synthetic polymers ( Gjorevski et al, 2016 ; Garreta et al, 2021 ) or even with biomaterials derived from decellularized extracellular matrix ( Cho et al, 2021 ; Kim et al, 2022 ). The synthetic polymers have the advantage of tunability, while the decellularized extracellular matrix shows similarity with molecular cues of native tissues.…”
Section: Organoids Recapitulating Models Of Diseasesmentioning
confidence: 99%
“…Several models have been developed ( He et al, 2020 ), including co-culture of human hepatic progenitor and stellate cells for the simulation of a fibrotic condition ( Leite et al, 2016 ). For drug testing these organoids must show metabolic competence, mostly evaluated by CYP induction and albumin secretion ( Kim et al, 2022 ). Recently, a bioprinted model of human hepatocyte-like cells derived from organoids was tested under exposition of a known hepatotoxic compound, showing an expected decrease in cell viability ( Bouwmeester et al, 2021 ).…”
Section: Organoids As Platforms For Drug Developmentmentioning
confidence: 99%
“…S3). To support the survival and maturation of ECs during the following period of mLO generation (16 days), we also optimized the DM previously used to produce liver organoids from liver tissue and iPSCs [ 37 39 ] by adding VEGF and bFGF [ 54 , 55 ]. mLOs were produced with or without HscLCs in ULA 96-well plates in DM for 5 days and further differentiated in ULA 24-well plates for 11 days using the same culture medium.…”
Section: Resultsmentioning
confidence: 99%
“…2 A. BG01-derived HEs, ECs, and HscLCs were dissociated into single-cell suspensions by treatment with TrypLE (12604-021, Gibco) for 3 min and collected using DMEM (12100-046, Gibco) containing 10% FBS (16000-044, Gibco). 1.5 × 10 4 HE, 3 × 10 4 ECs, and 5 × 10 3 HscLCs were seeded together in ultra-low attachment 96-well plates (ULA PrimeSurface® 96U, MS-9096UZ, SIMADZU) in cold multilineage liver organoid differentiation medium [ 37 40 ] [DM, advanced DMEM/F12 media supplemented with 1 × HEPES (15630-080, Gibco), 1 × GlutaMAX (35050-061, Gibco), 1 × penicillin/streptomycin (15140-122, Gibco), 0.1 mg/ml BSA (A7096, Sigma), 1 × B27 supplement minus vitamin A (12587-010, Gibco), 25 ng/ml BMP7 (120-03p, Peprotech), 100 ng/ml FGF19 (100-32, Peprotech), 25 ng/ml HGF (CYT-244, Prospec), 10 nM (Leu15)-Gastrin I (G9145, Sigma), 1.25 mM N-acetyl-L-cysteine (A9165, Sigma), 0.5 μM A83-01 (2939, Tocris Bioscience), 10 μM DAPT (ab120633, Abcam), 3 μM dexamethasone (D4902, Sigma), 0.566 mg/ml growth factor-reduced Matrigel (M354230, Corning), 100 ng/ml VEGF-165 (100-20, Peprotech), 50 ng/ml bFGF (100-18b, Peprotech), and 10 μM ROCK inhibitor Y27632 (1254, Tocris Bioscience)]. On days 1 and 3, cold DM was added to the organoid culture.…”
Section: Methodsmentioning
confidence: 99%