Liver tissue engineering and cell sources: issues and challenges

Abstract

Liver diseases are of major concern as they now account for millions of deaths annually. As a result of the increased incidence of liver disease, many patients die on the transplant waiting list, before a donor organ becomes available. To meet the huge demand for donor liver, alternative approaches using liver tissue engineering principles are being actively pursued. Even though adult hepatocytes, the primary cells of the liver are most preferred for tissue engineering of liver, their limited availability, isolation from diseased organs, lack of in vitro propagation and deterioration of function acts as a major drawback to their use. Various approaches have been taken to prevent the functional deterioration of hepatocytes including the provision of an adequate extracellular matrix and co-culture with non-parenchymal cells of liver. Great progress has also been made to differentiate human stem cells to hepatocytes and to use them for liver tissue engineering applications. This review provides an overview of recent challenges, issues and cell sources with regard to liver tissue engineering.

Long-term culture of human liver tissue with advanced hepatic functions

“…We have chosen to use human fetal liver cells to establish engineered liver tissues because they can be readily accessed from numerous sources and because the predominant parenchymal cells of fetal liver are hepatic stem cells and hepatoblasts, which are known to have excellent proliferative capability and the potential of hepatic differentiation in vitro (19,27,28). Indeed, the combination of unique characteristics of fetal liver cells and the ICC scaffold have allowed us to produce a 3D-engineered liver model with prolonged culture and advanced hepatic functionality.…”

“…The architectural features of the scaffold then enable the cells to self-assemble into a 3D configuration. The resulting cultures of primary human fetal liver cells were able to preserve advanced hepatic functions for extended periods of time (at least 5 months), a length of time that has not been achieved with any of the current in vitro liver models (18,19). Importantly, this engineered human liver tissue provided proof-of-concept determination of human-specific drug metabolism, demonstrated the ability to support infection with human hepatitis virus derived from an infected patient and subsequent antiviral drug testing against said infection, and facilitated detection of human-specific drug hepatotoxicity associated with late-onset liver failure.…”

Pluripotent stem cells to hepatocytes, the journey so far

“…Human ESCs and hiPSCs can undergo unlimited self-renewal, retaining their potential to differentiate into any type of somatic cell. This is a significant achievement, as these iPSCs can provide an inexhaustible human cell source (9).…”

“…However, the exact role of transcription factors and their mode of action during reprogramming remain elusive and puzzling. Following Yamanaka's reports (9,10), different groups have now successfully produced hiPSC cells using a variety of starting cell types, different combinations of transcription factors and different delivery techniques of these factors into the cells.…”

Low-Density Lipoprotein Uptake Demonstrates a Hepatocyte Phenotype in the Dog, but Is Nonspecific

“…There has been much interest in production of hepatocyte-like cells from stem cell sources [1]. In human medicine the resultant cells would be anticipated to have a variety of uses such as: transplantation, in bio-artificial liver devices to support patients until a transplant was available, or allow sufficient regeneration in cases of acute hepatic failure; as an in vitro model of liver disease; or as an in vitro system for modelling hepatic metabolism of candidate drugs [2].…”