Self-organization of hepatocyte morphogenesis depending on the size of collagen microbeads relative to hepatocytes
Name
manuscript_mohammad190409 Biofabrication_post-review.pdf
Description
Accepted version
Size
2.18 MB
Format
Adobe PDF
Checksum (MD5)
b824af7e5ec0a81b5233f68d3b1f68c1
Author(s)
Ajoudanian, Mohammad
Enomoto, Keita
Tokunaga, Yasuaki
Minami, Hiroshi
Chung, Seok
Tanishita, Kazuo
Kamm, Roger Dale
Sudo, Ryo
Date Issued
April 2019
Journal
Biofabrication
Publisher
IOP Publishing
Citation
Ajoudanian, Mohammad et al. "Self-organization of hepatocyte morphogenesis depending on the size of collagen microbeads relative to hepatocytes." Biofabrication 11, 3 (April 2019): 035007 © 2019 IOP Publishing Ltd
Version
Author's final manuscript
Abstract
Recent advances in microfabrication technologies have enabled us to construct collagen gel microbeads, which can be cultured with hepatocytes. However, little is known about the hepatocyte-collagen gel microbead interactions. Here, we aimed to clarify the effects of the balance between cell-cell and cell-collagen gel microbead interactions on hepatocyte morphogenesis and functions. The magnitude of cell-microbead interactions was controlled by changing the size of the microbeads, which were smaller than, comparable to, and larger than hepatocytes. These small, medium, and large microbeads were cultured separately with primary hepatocytes. Phase-contrast and time-lapse imaging revealed that the medium microbeads significantly induced the construction of 3D structures composed of the microbeads and hepatocytes in a self-organizing manner, whereas hepatocytes formed 2D monolayers with the small or large microbeads. These results suggest that only the medium microbeads induced the 3D tissue formation of hepatocytes. Furthermore, liver-specific functions, such as albumin secretion and ammonia clearance, were significantly upregulated in the 3D structures. These findings are critical to understand how to control the construction of 3D hepatocyte tissues with hydrogel microbeads in the context of biofabrication.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1088/1758-5090/ab145d
