Construction of three-dimensional vascularized functional human liver tissue using a layer-by-layer cell coating technique

Kazuki Sasaki, Takami Akagi, Tadafumi Asaoka, Hidetoshi Eguchi, Yasunari Fukuda, Yoshifumi Iwagami, Daisaku Yamada, Takehiro Noda, Hiroshi Wada, Kunihito Gotoh, Koichi Kawamoto, Yuichiro Doki, Masaki Mori, Mitsuru Akashi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The creation of artificial liver tissue is an active area of research due to the shortage of donors for liver transplantation. Here we investigated whether a simple and efficient cell coating technique developed in our laboratory could be used to generate functional vascularized liver tissue. This technique creates three-dimensional tissue by loading cells sterically onto other cells that have been coated with layer-by-layer (LbL) nanofilms of fibronectin and gelatin, two extracellular matrix proteins. We used this technique to construct homogenous, dense, well-vascularized liver tissue from cryopreserved human primary hepatocytes, human umbilical vein endothelial cells, and normal human dermal fibroblasts. Using LbL cell coating technique resulted in higher cellular function in terms of human albumin production (P < 0.01) and cytochrome P450 activity (P < 0.01) in vitro. Furthermore, after being transplanted subcutaneously into NOD/SCID mice, the vascularized liver tissue showed greater albumin production in the early stage than non-vascularized tissue or a hepatocyte suspension (P < 0.01). Histological examination demonstrated that compare to non-vascularized tissue, there were many less-morphologically changed and intact hepatocytes in the vascularized tissue. This cell coating technique would be applicable to the generation of vascularized functional liver tissue for regenerative medicine in the future.

Original languageEnglish
Pages (from-to)263-274
Number of pages12
JournalBiomaterials
Volume133
DOIs
Publication statusPublished - Jul 1 2017
Externally publishedYes

Fingerprint

Coating techniques
Liver
Tissue
Hepatocytes
Albumins
Artificial Liver
Inbred NOD Mouse
Regenerative Medicine
SCID Mice
Extracellular Matrix Proteins
Endothelial cells
Human Umbilical Vein Endothelial Cells
Fibroblasts
Gelatin
Fibronectins
Liver Transplantation
Cytochrome P-450 Enzyme System
Suspensions
Proteins
Skin

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Construction of three-dimensional vascularized functional human liver tissue using a layer-by-layer cell coating technique. / Sasaki, Kazuki; Akagi, Takami; Asaoka, Tadafumi; Eguchi, Hidetoshi; Fukuda, Yasunari; Iwagami, Yoshifumi; Yamada, Daisaku; Noda, Takehiro; Wada, Hiroshi; Gotoh, Kunihito; Kawamoto, Koichi; Doki, Yuichiro; Mori, Masaki; Akashi, Mitsuru.

In: Biomaterials, Vol. 133, 01.07.2017, p. 263-274.

Research output: Contribution to journalArticle

Sasaki, K, Akagi, T, Asaoka, T, Eguchi, H, Fukuda, Y, Iwagami, Y, Yamada, D, Noda, T, Wada, H, Gotoh, K, Kawamoto, K, Doki, Y, Mori, M & Akashi, M 2017, 'Construction of three-dimensional vascularized functional human liver tissue using a layer-by-layer cell coating technique', Biomaterials, vol. 133, pp. 263-274. https://doi.org/10.1016/j.biomaterials.2017.02.034
Sasaki, Kazuki ; Akagi, Takami ; Asaoka, Tadafumi ; Eguchi, Hidetoshi ; Fukuda, Yasunari ; Iwagami, Yoshifumi ; Yamada, Daisaku ; Noda, Takehiro ; Wada, Hiroshi ; Gotoh, Kunihito ; Kawamoto, Koichi ; Doki, Yuichiro ; Mori, Masaki ; Akashi, Mitsuru. / Construction of three-dimensional vascularized functional human liver tissue using a layer-by-layer cell coating technique. In: Biomaterials. 2017 ; Vol. 133. pp. 263-274.
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