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Inkjet-based 3D bioprinting
Published in Ali Khademhosseini, Gulden Camci-Unal, 3D Bioprinting in Regenerative Engineering, 2018
Shibu Chameettachal, Falguni Pati
Shu’s group used sodium alginate with hepatocytes derived from human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) as bioink to print with a microvalve bioprinter, a class of DBB to fabricate 3D liver tissue models (Faulkner-Jones et al. 2015). In this study, alternate layers of the bioink and calcium chloride cross-linker were co-printed to facilitate the alginate cross-linking. After 17 days of post-bioprinting, cells were differentiated and hepatic markers such as hepatocyte nuclear factor 4 alpha (HNF4a), a transcription factor that regulates the expression of hepatic genes, were demonstrated along with albumin.
Applications of Pluripotent Stem Cells in the Therapy and Modeling of Diabetes and Metabolic Diseases
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
Suranjit Mukherjee, Shuibing Chen
Using the hepatocytes derived from iPSCs of T2DM, MODY1, or MODY2, patients can help reveal new disease mechanisms within the context of the liver. For example, MODY1 patients carry mutations in the HNF4α gene that plays critical roles in β cell as well as hepatic development. MODY2 patients are characterized by mutations in the glucokinase gene and exhibit impaired hepatic glycogen synthesis concomitant with augmented hepatic gluconeogenesis. Modeling these mutations within hiPSC-derived hepatocytes provides opportunities to explore how HNF4α and glucokinase affect hepatocyte development and glucose metabolism.
Genetic toxicity assessment using liver cell models: past, present, and future
Published in Journal of Toxicology and Environmental Health, Part B, 2020
Xiaoqing Guo, Ji-Eun Seo, Xilin Li, Nan Mei
HepG2 transformants expressing various major CYP450 isoforms, such as CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4, were evaluated for their suitability for genotoxicity assessment in the MNvit assay using two indirect-acting genotoxicants, B[a]P and CPA. B[a]P and CPA produced a marked elevation in MN frequencies in CYP1A2 and CYP2C9 transformants, respectively (Hashizume et al. 2009). By utilizing HepG2 transformants, okadaic acid and β-endosulfan, two newly developed drugs, were found to exert genotoxicity via CYP1A2- and CYP3A4-mediated pathway, respectively (Hashizume et al. 2009, 2010). In addition, human-induced hepatocytes (hiHeps), generated from fibroblasts by lentiviral expression of three liver transcription factors (FOXA3, HNF1A, and HNF4A), were noted as a novel cell model possessing functional characteristics of mature hepatocytes, including CYP450 enzyme activities and biliary drug clearance (Huang et al. 2014). hiHeps exhibited a high sensitivity in detecting the MN induction of six clastogens, namely, N-nitrosodiethylamine (DEN), MMS, 2-NF, B[a]P, AFB1, and CPA, suggesting a potential application for in vitro genotoxicity assessment (Liu et al. 2019).
Regulation of cytochrome P450 expression by microRNAs and long noncoding RNAs: Epigenetic mechanisms in environmental toxicology and carcinogenesis
Published in Journal of Environmental Science and Health, Part C, 2019
Dongying Li, William H. Tolleson, Dianke Yu, Si Chen, Lei Guo, Wenming Xiao, Weida Tong, Baitang Ning
A variety of factors influence CYP expression. Genetic variations, including single nucleotide polymorphisms (SNPs), copy number variations (CNVs), and pseudogenes, have been shown to affect CYP expression and CYP-related cancers.26–28 Transcription factors, co-activators and co-repressors, and nuclear receptors (NRs) are key transcriptional regulators of CYP expression. Hepatic nuclear factor (HNF) 1 A and HNF4A are important regulators of CYP expression, as are the xenobiotic sensor receptors, such as pregnane X receptor (PXR), constitutive androstane receptor (CAR), aryl hydrocarbon receptor (AhR), and vitamin D receptor (VDR), which can activate CYP expression.29