Metabolic Patterning on a Chip: Towards in vitro Liver Zonation of Primary Rat and Human Hepatocytes
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An important number of healthy and diseased tissues shows spatial variations in their metabolic capacities across the tissue. The liver is a prime example of such heterogeneity where the gradual changes in various metabolic activities across the liver sinusoid is termed as “zonation” of the liver. Here, we introduce the Metabolic Patterning on a Chip (MPOC) platform capable of dynamically creating metabolic patterns across the length of a microchamber of liver tissue via actively enforced gradients of various metabolic modulators such as hormones and inducers. Using this platform, we were able to create continuous liver tissues of both rat and human origin with gradually changing metabolic activities. The gradients we have created in nitrogen, carbohydrate and xenobiotic metabolisms recapitulated an in vivo like zonation and zonal toxic response. Beyond its application in recapitulation of liver zonation in vitro as we demonstrate here, the MPOC platform can be used and expanded for a variety of purposes including better understanding of heterogeneity in many different tissues during developmental and adult stages.
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Partially zonated metabolism has been established in vitro.
“Although partially zonated metabolism has been established in vitro,[168], [169], [170]”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [169]
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- Authors
- Kang, Y. B., Eo, J., Mert, S., Yarmush, M. L., & Usta, O. B.
- Affiliations
- Harvard University (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Usta, O. Berk
- Venue
- Scientific Reports
- Published
- 2018-06-12
- Volume
- 8
- Issue
- 1
- Pages
- 8951-8951
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5997652
- OpenAlex
- W2805101331
- Cited by
- 122
- References
- 60
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 6 · 2023: 25 · 2022: 24 · 2021: 10 · 2020: 20 · 2019: 12 · 2018: 4
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Digital Commons - George Fox University (George Fox University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering (R01EB023812, R21EB020192, P41EB002503)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- liver zonation, hepatocyte zonation, metabolic gradients, hepatocyte heterogeneity, xenobiotic metabolism, nitrogen metabolism, carbohydrate metabolism, primary human hepatocytes, rat hepatocytes, tissue engineering
- MeSH terms
- Animals, Female, Humans, Liver, Rats, Inbred Lew, Xenobiotics, Hepatocytes, Carbohydrate Metabolism, Rats, Primary Cell Culture
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