The generation of functionally differentiated, three-dimensional hepatic tissue from two-dimensional sheets of progenitor small hepatocytes and nonparenchymal cells

Transplantation
Kohei OgawaJ P Vacanti

Abstract

The authors' laboratory has investigated tissue engineering of the liver as a novel approach for treating end-stage liver disease. Fabrication of thick, viable, three-dimensional liver tissue is limited by the lack of vascularity in the tissue-engineered constructs. To overcome this limitation, the authors fabricated three-dimensional, vascularized liver tissue in vivo from two-dimensional cell sheets created from small hepatocytes (SHC) and nonparenchymal cells (NPC) implanted into rat omentum. SHC and NPC were cultured on a silicon wafer and lifted as monolayer cell sheets. After maximal hepatotrophic stimulation was induced in the host by injecting retrorsine, creating a portacaval shunt, and performing a partial hepatectomy, these sheets were placed onto the omentum and then rolled into a three-dimensional cylinder. New tissue consisting of both hepatocytes and bile duct-like structures formed by 2 weeks, and the mass of hepatocytes increased in size up to 2 months. The hepatocytes in these constructs were immunohistochemically positive for albumin and transferrin, and bile duct-like structures were positive for gamma-glutamyl transpeptidase, which suggests that they possess liver-specific function. Electron microscopy also...Continue Reading

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Citations

May 24, 2007·Tissue Engineering·Lisa E FreedGordana Vunjak-Novakovic
Jun 6, 2009·Journal of Dental Research·S A Hacking, A Khademhosseini
Apr 23, 2008·Pediatric Research·David M HogansonJoseph P Vacanti
Jul 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·Alison P McGuigan, Michael V Sefton
Jan 24, 2007·Stem Cell Reviews·Curtis L Cetrulo
Jul 31, 2013·Journal of Biomedical Materials Research. Part a·Costantino Del GaudioPaolo Macchiarini
Jan 22, 2017·Journal of Tissue Engineering and Regenerative Medicine·Mio FujiiSusumu Eguchi
Aug 19, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ryo SudoKazuo Tanishita

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