A novel formulation of oxygen‐carrying matrix enhances liver‐specific function of cultured hepatocytes
Abstract
Oxygen is an important component of the cellular microenvironment, mediating cell survival, differentiation, and function. Oxygen supply is a limiting factor during culture of highly metabolic cells such as hepatocytes. Here we present a simple formulation of a fluorocarbon-based oxygen carrier embedded in collagen gel that increases oxygen concentration in culture 6-fold. Rat hepatocytes cultured on oxygen carrier-collagen showed a significant increase in viability and function. Cytochrome P450IA1 activity was increased by 140% in serum-free cultures and by 820% in serum-containing cultures. The significantly higher hepatocellular function on oxygen carrier-collagen matrix persisted and increased during long-term culture. Long-term albumin secretion was increased by 350% in serum-free cultures and by 166% in serum-containing culture. Long-term urea secretion was increased by 79% in serum-free cultures and by 76% in serum-containing cultures. We conclude that oxygen supply may limit hepatocyte function in vitro. This limitation can be overcome by addition of an oxygen carrier to the extracellular matrix. Culture of hepatocytes on oxygen-carrying matrix mimics the oxygen-rich environment of the liver and provides a simple method for enhanced long-term function.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Oxygen is crucially supplied to hepatocytes by the mixing of arterial and venous blood in sinusoids at a rate of ∼1.2 nmol/s/10^6 cells to meet the oxygen demand and support the high metabolic activity of hepatocytes.
“Oxygen is crucially supplied to hepatocytes by the mixing of arterial (hepatic artery) and venous blood (portal vein) in sinusoids at a rate of ∼1.2 nmol/s/106 cells to meet the oxygen demand and support the high metabolic activity of hepatocytes [224].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [224]
Cites
Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue
Radisic, M., Malda, J., Epping, E., Geng, W., Langer, R., & Vunjak‐Novakovic, G. (2006) · Biotechnology and Bioengineering · doi:10.1002/bit.20722 · Cited by 399 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280 · see citing works
Badylak, S. F., Taylor, D., & Uygun, K. (2011) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071910-124743 · Cited by 1,041 · see citing works
Yamada, M., Utoh, R., Ohashi, K., Tatsumi, K., Yamato, M., Okano, T., & Seki, M. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.07.068 · Cited by 247 · see citing works
Challenges and Opportunities in the Design of Liver-on-Chip Microdevices
Ehrlich, A., Duche, D., Ouedraogo, G., & Nahmias, Y. (2019) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-060418-052305 · Cited by 125 · see citing works
Self-citationHussein, K. H., Ahmadzada, B., Correa, J. C., Sultan, A., Wilken, S., Amiot, B., & Nyberg, S. L. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.06.001 · Cited by 28 · see citing works
“Oxygen is crucially supplied to hepatocytes by the mixing of arterial (hepatic artery) and venous blood (portal vein) in sinusoids at a rate of ~1.2 nmol/s/10 6 cells to meet the oxygen demand and support the high metabolic activity of hepatocytes [224].”
BackgroundInfluential
- Authors
- Nahmias, Y., Kramvis, Y., Barbe, L., Casali, M., Berthiaume, F., Yarmush, M. L., Nahmias, Y., Kramvis, Y., Barbe, L., Casali, M., Berthiaume, F., & Yarmush, M. L.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2006-10-31
- Volume
- 20
- Issue
- 14
- Pages
- 2531-2533
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2047220333
- Cited by
- 81
- References
- 1
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 7 · 2012: 5
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- oxygen carriers, fluorocarbons, collagen gel, hepatocyte culture, oxygen supply, hepatocyte viability, cytochrome P450IA1, albumin secretion, urea secretion, extracellular matrix, liver-specific function
- MeSH terms
- Serum Albumin, Human, Animals, Cells, Cultured, Collagen, Culture Media, Cytochrome P-450 Enzyme System, Female, Oxygen, Partial Pressure, Rats, Inbred Lew, Serum Albumin, Urea, Cell Culture Techniques, Hepatocytes, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
