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Modular assembly-based approach of loosely packing co-cultured hepatic tissue elements with endothelialization for liver tissue engineering
Journal article   Open access

Modular assembly-based approach of loosely packing co-cultured hepatic tissue elements with endothelialization for liver tissue engineering

Jianyu He, Yuan Pang, Huayu Yang, Kevin Montagne, Marie Shinohara, Yilei Mao, Wei Sun and Yasuyuki Sakai
Annals of translational medicine, v 8(21), pp 1400-1400
01 Nov 2020
DOI: https://doi.org/10.21037/atm-20-1598
PMID: 33313145
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.21037/atm-20-1598View
Published, Version of Record (VoR)CC BY-NC-ND V4.0,  Open

Abstract

Life Sciences & Biomedicine Medicine, Research & Experimental Oncology Research & Experimental Medicine Science & Technology
Background: In liver tissue engineering, co-culturing hepatocytes with typical non-parenchymal hepatic cells to form cell aggregates is available to mimic the in vivo microenvironment and promote cell biological functions. With a modular assembly approach, endothelialized hepatic cell aggregates can be packed for perfusion culture, which enables the construction of large-scale liver tissues. Since tightly packed aggregates tend to fuse with each other and block perfusion flows, a loosely packed mode was introduced in our study. Methods: Using an oxygen-permeable polydimethylsiloxane (PDMS)-based microwell device, highly dense endothelialized hepatic cell aggregates were generated as hepatic tissue elements by co-culturing hepatocellular carcinoma (HepG2) cells, Swiss 3T3 cells, and human umbilical vein endothelial cells (HUVECs). The co-cultured aggregates were then harvested and applied in a PDMS-fabricated bioreactor for 10 days of perfusion culture. To maintain appropriate interstitial spaces for stable perfusion, biodegradable poly-L-lactic acid (PLLA) scaffold fibers were used and mixed with the aggregates, forming a loosely packed mode. Results: In a microwell co-culture, Swiss 3T3 cells significantly contributed to the formation of hepatic cell aggregates. HUVECs developed a peripheral distribution in aggregates for endothelialization. In the perfusion culture, compared with pure HepG2 aggregates, HepG2/Swiss 3T3/HUVECs co-cultured aggregates exhibited a higher level of cell proliferation and liver-specific function expression (i.e., glucose consumption and albumin secretion). Under the loosely packed mode, co-cultured aggregates showed a characteristic histological morphology with cell migration and adhesion to fibers. The assembled hepatic tissue elements were obtained with 32% of in vivo cell density. Conclusions: In a co-culture of HepG2, Swiss 3T3, and HUVECs, Swiss 3T3 cells were observed to be beneficial for the formation of endothelialized hepatic cell aggregates. Loosely packed aggregates enabled long-term perfusion culture with high viability and biological function. This study will guide us in constructing large-scale liver tissue models by way of aggregate-based modular assembly.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Medicine, Research & Experimental
Oncology
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