Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.biomaterials.2011.12.006
Title: Tethered spheroids as an invitro hepatocyte model for drug safety screening
Authors: Xia, L.
Sakban, R.B.
Qu, Y.
Hong, X.
Zhang, W. 
Nugraha, B.
Tong, W.H.
Ananthanarayanan, A.
Zheng, B.
Chau, I.Y.Y.
Jia, R.
McMillian, M.
Silva, J.
Dallas, S.
Yu, H. 
Keywords: 3D hepatocyte model
CYP450 enzymes
Drug safety testing
Galactose
RGD
Xenobiotics
Issue Date: Mar-2012
Citation: Xia, L., Sakban, R.B., Qu, Y., Hong, X., Zhang, W., Nugraha, B., Tong, W.H., Ananthanarayanan, A., Zheng, B., Chau, I.Y.Y., Jia, R., McMillian, M., Silva, J., Dallas, S., Yu, H. (2012-03). Tethered spheroids as an invitro hepatocyte model for drug safety screening. Biomaterials 33 (7) : 2165-2176. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biomaterials.2011.12.006
Abstract: Hepatocyte spheroids mimic many invivo liver-tissue phenotypes but increase in size during extended culture which limits their application in drug testing applications. We have developed an improved hepatocyte 3D spheroid model, namely tethered spheroids, on RGD and galactose-conjugated membranes using an optimized hybrid ratio of the two bioactive ligands. Cells in the spheroid configuration maintained 3D morphology and uncompromised differentiated hepatocyte functions (urea and albumin production), while the spheroid bottom was firmly tethered to the substratum maintaining the spheroid size in multi-well plates. The oblate shape of the tethered spheroids, with an average height of 32μm, ensured efficient nutrient, oxygen and drug access to all the cells within the spheroid structure. Cytochrome P450 induction by prototypical inducers was demonstrated in the tethered spheroids and was comparable or better than that observed with hepatocyte sandwich cultures. These data suggested that tethered 3D hepatocyte spheroids may be an excellent alternative to 2D hepatocyte culture models for drug safety applications. © 2011 Elsevier Ltd.
Source Title: Biomaterials
URI: http://scholarbank.nus.edu.sg/handle/10635/112813
ISSN: 01429612
DOI: 10.1016/j.biomaterials.2011.12.006
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