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Biofabrication ofsize?controlled liver microtissues incorporated withECM?derived microparticles toprolong hepatocyte function
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ZahraHeydari, IbrahimZarkesh, Mohammad?HosseinGhanian, MahdokhtH.Aghdaei, SvetlanaKotova, EnsiehZahmatkesh, ZahraFarzaneh, AbbasPiryaei, ImanAkbarzadeh, AnastasiaShpichka, RobertoGramignoli, PeterTimashev, HosseinBaharvand, MassoudVosough. Biofabrication ofsize?controlled liver microtissues incorporated withECM?derived microparticles toprolong hepatocyte function[J]. Journal of Zhejiang University Science D, 2021, 4(4): 790-805.
@article{title="Biofabrication ofsize?controlled liver microtissues incorporated withECM?derived microparticles toprolong hepatocyte function",
author="ZahraHeydari, IbrahimZarkesh, Mohammad?HosseinGhanian, MahdokhtH.Aghdaei, SvetlanaKotova, EnsiehZahmatkesh, ZahraFarzaneh, AbbasPiryaei, ImanAkbarzadeh, AnastasiaShpichka, RobertoGramignoli, PeterTimashev, HosseinBaharvand, MassoudVosough",
journal="Journal of Zhejiang University Science D",
volume="4",
number="4",
pages="790-805",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1007/s42242-021-00137-4"
}
%0 Journal Article
%T Biofabrication ofsize?controlled liver microtissues incorporated withECM?derived microparticles toprolong hepatocyte function
%A ZahraHeydari
%A IbrahimZarkesh
%A Mohammad?HosseinGhanian
%A MahdokhtH.Aghdaei
%A SvetlanaKotova
%A EnsiehZahmatkesh
%A ZahraFarzaneh
%A AbbasPiryaei
%A ImanAkbarzadeh
%A AnastasiaShpichka
%A RobertoGramignoli
%A PeterTimashev
%A HosseinBaharvand
%A MassoudVosough
%J Journal of Zhejiang University SCIENCE D
%V 4
%N 4
%P 790-805
%@ 1869-1951
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1007/s42242-021-00137-4
TY - JOUR
T1 - Biofabrication ofsize?controlled liver microtissues incorporated withECM?derived microparticles toprolong hepatocyte function
A1 - ZahraHeydari
A1 - IbrahimZarkesh
A1 - Mohammad?HosseinGhanian
A1 - MahdokhtH.Aghdaei
A1 - SvetlanaKotova
A1 - EnsiehZahmatkesh
A1 - ZahraFarzaneh
A1 - AbbasPiryaei
A1 - ImanAkbarzadeh
A1 - AnastasiaShpichka
A1 - RobertoGramignoli
A1 - PeterTimashev
A1 - HosseinBaharvand
A1 - MassoudVosough
J0 - Journal of Zhejiang University Science D
VL - 4
IS - 4
SP - 790
EP - 805
%@ 1869-1951
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1007/s42242-021-00137-4
Abstract: Multicellular microtissues of primary human hepatocytes (PHHs) co-cultured with other supporting cell types are a promising model for drug screening and toxicological studies. However, these liver microtissues (LMs) rapidly lose their functions
during exvivo culture. Here, in order to mimic the cellular and structural hepatic microenvironment, we co-cultured PHHs
with human mesenchymal stromal cells (MSCs) and human umbilical vein endothelial cells (HUVECs) in the presence of
cell-sized microparticles (MPs) derived from liver extracellular matrix (LEMPs). The microwell culture platform enabled
biofabrication of size-controlled multicellular microtissues (PHH:HUVEC:MSC=3:2:1) with efcient LEMP incorporation (about 70% at a 2:1 ratio of cells:MP). The biofabricated liver microtissues (BLMs) were cultured exvivo for 14days
and compared to the cell-only LM in terms of gene and protein expression, functional activity, cytochrome P450 (CYP450)
enzyme inducibility, and drug sensitivity. The results supported superior hepatic-related gene expression, functional activity, and polarity for PHH in BLM compared to LM. CYP450 enzyme inducibility and dose-responsive sensitivity to toxic
drugs were signifcantly higher in the BLM group. In conclusion, microtissue engineering by incorporation of tissue-specifc
microparticles within a multicellular microtissue can ofer some advantages for drug discovery studies and cell transplantation applications. In the near future, this approach could generate a scalable platform of several functional biofabricated
microtissues representing diferent organs.
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