Engineering of an hepatic organoid to develop liver assist devices

Alejandro Soto-Gutierrez, Nalú Navarro-Alvarez, Hiroshi Yagi, Yakoov Nahmias, Martin L. Yarmush, Naoya Kobayashi

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Cell-based technologies to support/restore liver function represent one of the most promising opportunities in the treatment of acute liver failure. However, the understanding of the constituent cell types that interact to achieve liver-specific structure and function has not been achieved in the development of liver assist devices (LADs). Here we show that hepatocytes migrated toward and adhered and formed sinusoids-like structures in conjunction with liver nonparenchymal cells, and that this liver organoid formed sophisticated tissue after 7 days in an implanted LAD in rodents. Hepatocytes only or in combination with human nonparenchymal liver cell lines (endothelial, cholangiocytes, and stellate cells) were cultured in Matrigel. Ultrastructural analysis showed that the hepatocyte-decorated endothelial vascular structures resemble in vivo sinusoids containing plate-like structures, bile canaliculi, and lumen. The sinusoid-like structures retained albumin secretion and drug metabolism capabilities. In addition, LADs containing cocultures of human liver nonparenchymal cells were transplanted in animals for a week; the liver tissue formed sophisticated structures resembling the liver. These results demonstrate the importance of nonparenchymal cells in the cellular composition of LADs. The novelty of the culture's sinusoid-like organization and function strongly support the integration of liver nonparenchymal units into hepatocyte coculture-based LADs as a potential destination therapy for liver failure.

Original languageEnglish
Pages (from-to)815-822
Number of pages8
JournalCell Transplantation
Volume19
Issue number6-7
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

Organoids
Liver
Equipment and Supplies
Hepatocytes
Coculture Techniques
Bile Canaliculi
Tissue
Acute Liver Failure
Liver Failure

Keywords

  • Liver cell therapy
  • Liver failure
  • Liver support
  • Organoid

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Soto-Gutierrez, A., Navarro-Alvarez, N., Yagi, H., Nahmias, Y., Yarmush, M. L., & Kobayashi, N. (2010). Engineering of an hepatic organoid to develop liver assist devices. Cell Transplantation, 19(6-7), 815-822. https://doi.org/10.3727/096368910X508933

Engineering of an hepatic organoid to develop liver assist devices. / Soto-Gutierrez, Alejandro; Navarro-Alvarez, Nalú; Yagi, Hiroshi; Nahmias, Yakoov; Yarmush, Martin L.; Kobayashi, Naoya.

In: Cell Transplantation, Vol. 19, No. 6-7, 2010, p. 815-822.

Research output: Contribution to journalArticle

Soto-Gutierrez, A, Navarro-Alvarez, N, Yagi, H, Nahmias, Y, Yarmush, ML & Kobayashi, N 2010, 'Engineering of an hepatic organoid to develop liver assist devices', Cell Transplantation, vol. 19, no. 6-7, pp. 815-822. https://doi.org/10.3727/096368910X508933
Soto-Gutierrez A, Navarro-Alvarez N, Yagi H, Nahmias Y, Yarmush ML, Kobayashi N. Engineering of an hepatic organoid to develop liver assist devices. Cell Transplantation. 2010;19(6-7):815-822. https://doi.org/10.3727/096368910X508933
Soto-Gutierrez, Alejandro ; Navarro-Alvarez, Nalú ; Yagi, Hiroshi ; Nahmias, Yakoov ; Yarmush, Martin L. ; Kobayashi, Naoya. / Engineering of an hepatic organoid to develop liver assist devices. In: Cell Transplantation. 2010 ; Vol. 19, No. 6-7. pp. 815-822.
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