Self-organization of hepatocyte morphogenesis depending on the size of collagen microbeads relative to hepatocytes

Mohammad Ajoudanian, Keita Enomoto, Yasuaki Tokunaga, Hiroshi Minami, Seok Chung, Kazuo Tanishita, Roger D. Kamm, Ryo Sudo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Number of pages1
JournalBiofabrication
Volume11
Issue number3
DOIs
Publication statusPublished - 2019 Apr 26

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Microspheres
Morphogenesis
Collagen
Hepatocytes
Gels
Tissue
Time-Lapse Imaging
Hydrogel
Microtechnology
Microfabrication
Ammonia
Hydrogels
Liver
Albumins
Monolayers
Cell Communication
Imaging techniques
Technology

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

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Self-organization of hepatocyte morphogenesis depending on the size of collagen microbeads relative to hepatocytes. / Ajoudanian, Mohammad; Enomoto, Keita; Tokunaga, Yasuaki; Minami, Hiroshi; Chung, Seok; Tanishita, Kazuo; Kamm, Roger D.; Sudo, Ryo.

In: Biofabrication, Vol. 11, No. 3, 26.04.2019.

Research output: Contribution to journalArticle

Ajoudanian, Mohammad ; Enomoto, Keita ; Tokunaga, Yasuaki ; Minami, Hiroshi ; Chung, Seok ; Tanishita, Kazuo ; Kamm, Roger D. ; Sudo, Ryo. / Self-organization of hepatocyte morphogenesis depending on the size of collagen microbeads relative to hepatocytes. In: Biofabrication. 2019 ; Vol. 11, No. 3.
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