The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes
Open accessAbstract
BACKGROUND & AIMS: Hepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs from multiple lineages, using two different protocols, for direct comparison with fresh fetal and adult hepatocytes. METHODS: Protocols were developed for robust differentiation. Multiple transcript, protein and functional analyses compared HLCs to fresh human fetal and adult hepatocytes. RESULTS: HLCs were comparable to those of other laboratories by multiple parameters. Transcriptional changes during differentiation mimicked human embryogenesis and showed more similarity to pericentral than periportal hepatocytes. Unbiased proteomics demonstrated greater proximity to liver than 30 other human organs or tissues. However, by comparison to fresh material, HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype. The expression of 81% phase 1 enzymes in HLCs was significantly upregulated and half were statistically not different from fetal hepatocytes. HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. In seven bespoke tests, devised by principal components analysis to distinguish fetal from adult hepatocytes, HLCs from two different source laboratories consistently demonstrated fetal characteristics. CONCLUSIONS: HLCs from different sources are broadly comparable with unbiased proteomic evidence for faithful differentiation down the liver lineage. This current phenotype mimics human fetal rather than adult hepatocytes.
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Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells
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Generation of Functional Human Hepatic Endoderm From Human Induced Pluripotent Stem Cells
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HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells
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Penney, J., Ralvenius, W. T., & Tsai, L.-H. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0468-3 · Cited by 471
Modeling human diseases with induced pluripotent stem cells: from 2D to 3D and beyond
Liu, C., Oikonomopoulos, A., Sayed, N., & Wu, J. C. (2018) · Development · doi:10.1242/dev.156166 · Cited by 267
Human hepatocyte transplantation for liver disease: current status and future perspectives
Iansante, V, Mitry, R. R., Filippi, C., Fitzpatrick, E., & Dhawan, A. (2018) · Pediatric Research · doi:10.1038/pr.2017.284 · Cited by 225
Lauschke, V. M., Hendriks, D. F. G., Bell, C. C., Andersson, T. B., & Ingelman-Sundberg, M. (2016) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.6b00150 · Cited by 241
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Metadata
- Authors
- Baxter, M., Withey, S., Harrison, S., Segeritz, C.-P., Zhang, F., Atkinson-Dell, R., Rowe, C., Gerrard, D. T., Sison-Young, R., Jenkins, R., Henry, J., Berry, A. A., Mohamet, L., Best, M., Fenwick, S. W., Malik, H., Kitteringham, N. R., Goldring, C. E., Piper Hanley, K., Vallier, L., & Hanley, N. A.
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 62
- Issue
- 3
- Pages
- 581-589
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2120057036
- Cited by
- 348
- References
- 5
- FWCI
- 8.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Baxter, M., Withey, S., Harrison, S., Segeritz, C.-P., Zhang, F., Atkinson-Dell, R., Rowe, C., Gerrard, D. T., Sison-Young, R., Jenkins, R., Henry, J., Berry, A. A., Mohamet, L., Best, M., Fenwick, S. W., Malik, H., Kitteringham, N. R., Goldring, C. E., Piper Hanley, K., . . . Hanley, N. A. (2015). Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes. Journal of Hepatology. https://doi.org/10.1016/j.jhep.2014.10.016
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