Transplantation of Liver Organoids in the Omentum and Kidney

Abstract

Liver organoids were reconstructed by mouse-immortalized hepatocytes and nonparenchymal cells (sinusoidal endothelial cells and hepatic stellate cells) in a radial-flow bioreactor (RFB). A biodegradable apatite-fiber scaffold (AFS) was used as a scaffold packed in the RFB, which enables three-dimensional cell cultures. The organoids cocultured in the RFB showed a liver-like structure with high-density layers of hepatocytes and the formation of vessel-like structures. A liver organoid consisting of three cocultured cells was transplanted under the kidney capsule (kidney group) or into the omentum (omentum group) using BALB/c nude mice. Transplanted liver organoids survived in the kidney or omentum. The expression of mRNAs of albumin, connexin 26 and 32, hepatocyte nuclear factor 4α, and glucose-6-phosphatase was increased in both groups at 8 weeks after transplantation in comparison to the pretransplant status. Tyrosine aminotransferase appeared only in the omentum group. The results suggested that the functions of liver organoids differed depending on the transplanted site in the recipient animals.

Liver Regeneration

“…When hepatocytes mixed in the ECM obtained from murine EngelbrethÀHolmÀSwarm tumor cell lines gel were transplanted under the bilateral kidney capsule spaces, they resulted in a liver tissue formation that possessed active regeneration potential [171,172]. In a more recent study, 3D liver organoids comprised of hepatocytes and nonparenchymal cells (sinusoidal endothelial cells and hepatic stellate cells) were transplanted under kidney capsule and showed enhanced hepatic functions and survival for 8 weeks after transplantation [173].…”

Epithelial Cell Coculture Models for Studying Infectious Diseases: Benefits and Limitations

“…A coculture model of alveolar epithelial cells with monocyte-derived macrophages and dendritic cells, for example, has been used to model alveolar epithelial barriers to microorganisms [19]. Expansion of cocultures through the use of structurally distinct 3D organotypic systems [20, 21] is another area of intense research gaining popularity. These systems utilize free flowing media and complex scaffolds in radial-flow or rotating wall bioreactors.…”

“…These systems utilize free flowing media and complex scaffolds in radial-flow or rotating wall bioreactors. This approach more closely replicates in vivo biology beyond basic coculturing of different cell types with rearrangement of cells into proto-organic structures [20, 21]. Moreover, recent data indicate that these systems offer new ways to study signalling events and drug interactions [21].…”

“…In studies focused on liver, the use of immortalized hepatic and sinusoidal cell lines was combined in a radial flow bioreactor to replicate part of a lobe [62]. Studies of byproducts from these synthetic liver organoids have yielded varying results but so far indicate some key synergistic effects for drug metabolism, albumin, and urea production [20, 61, 62, 67]. …”

Liver Regenerative Medicine: Advances and Challenges

“…These engineered structures were viable for 3 weeks [Linke et al, 2007]. Using a biodegradable apatite-fiber scaffold, Saito et al [2011] reported the generation of the liver organoid reconstructed by mouse-immortalized hepatocytes and nonparenchymal cells (sinusoidal endothelial cells and hepatic stellate cells) in a radial-flow bioreactor. After transplantation, the organoid that had a liver-like structure with high-density layers of hepatocytes and vessel-like structures successfully survived in the omentum and kidney of recipient mice.…”