Recellularization of rat liver: An in vitro model for assessing human drug metabolism and liver biology

Matthew J. Robertson, Benjamin Soibam, Jacqueline G. O’Leary, Luiz C. Sampaio, Doris A. Taylor

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Liver-like organoids that recapitulate the complex functions of the whole liver by combining cells, scaffolds, and mechanical or chemical cues are becoming important models for studying liver biology and drug metabolism. The advantages of growing cells in three-dimensional constructs include enhanced cell-cell and cell-extracellular matrix interactions and preserved cellular phenotype including, prevention of de-differentiation. In the current study, biomimetic liver constructs were made via perfusion decellularization of rat liver, with the goal of maintaining the native composition and structure of the extracellular matrix. We optimized our decellularization process to produce liver scaffolds in which immunogenic residual DNA was removed but glycosaminoglycans were maintained. When the constructs were recellularized with rat or human liver cells, the cells remained viable, capable of proliferation, and functional for 28 days. Specifically, the cells continued to express cytochrome P450 genes and maintained their ability to metabolize a model drug, midazolam. Microarray analysis showed an upregulation of genes involved in liver regeneration and fibrosis. In conclusion, these liver constructs have the potential to be used as test beds for studying liver biology and drug metabolism.

Original languageEnglish (US)
Article numbere0191892
JournalPLoS One
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2018

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Metabolism
Liver
pharmacokinetics
Rats
Biological Sciences
liver
rats
Pharmaceutical Preparations
cells
extracellular matrix
Scaffolds (biology)
Extracellular Matrix
liver regeneration
biomimetics
Organoids
Genes
liver cirrhosis
In Vitro Techniques
glycosaminoglycans
Biomimetics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Recellularization of rat liver : An in vitro model for assessing human drug metabolism and liver biology. / Robertson, Matthew J.; Soibam, Benjamin; O’Leary, Jacqueline G.; Sampaio, Luiz C.; Taylor, Doris A.

In: PLoS One, Vol. 13, No. 1, e0191892, 01.01.2018.

Research output: Contribution to journalArticle

Robertson, Matthew J. ; Soibam, Benjamin ; O’Leary, Jacqueline G. ; Sampaio, Luiz C. ; Taylor, Doris A. / Recellularization of rat liver : An in vitro model for assessing human drug metabolism and liver biology. In: PLoS One. 2018 ; Vol. 13, No. 1.
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