Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids

Abstract

To replicate functional liver tissue in vitro for drug testing or transplantation, 3D tissue engineering requires representative cell models as well as scaffolds that not only promote tissue production but also are applicable in a clinical setting. Recently, adult liver‐derived liver organoids are found to be of much interest due to their genetic stability, expansion potential, and ability to differentiate toward a hepatocyte‐like fate. The current standard for culturing these organoids is a basement membrane hydrogel like Matrigel (MG), which is derived from murine tumor material and apart from its variability and high costs, possesses an undefined composition and is therefore not clinically applicable. Here, a cellulose nanofibril (CNF) hydrogel is investigated with regard to its potential to serve as an alternative clinical grade scaffold to differentiate liver organoids. The results show that its mechanical properties are suitable for differentiation with overall, either equal or improved, functionality of the hepatocyte‐like cells compared to MG. Therefore, and because of its defined and tunable chemical definition, the CNF hydrogel presents a viable alternative to MG for liver tissue engineering with the option for clinical use.

Scaffolds obtained from decellularized human extrahepatic bile ducts support organoids to establish functional biliary tissue in a dish

“…To overcome this “hurdle,” clinically relevant and well‐defined culture substrates are required. Alternative candidates have already been investigated for organoids cultures (Giobbe et al, 2019; Gjorevski et al, 2016; Krüger et al, 2020).…”

Composition and Mechanism of Three-Dimensional Hydrogel System in Regulating Stem Cell Fate

“…104,148,236,237 Compared with Matrigel, cellulose nanofibril hydrogel performed equally for hepatic differentiation of liver-derived adult stem cells in an organoid culture because of the rapid shear-thinning and self-healing behavior. 238 Moreover, a composited hydrogel based on PEG hydrogel and gelatin hydrogel immobilized with ECMderived proteins efficiently promoted MSC vasculogenic and osteogenic differentiation. This versatile platform has been found to be superior to the Matrigel model in engineering organ analogues, including prevascularized bone constructs and liver organoid, because of the customizability of covalent immobilization of tissue-specific proteins.…”

Human liver model systems in a dish

“…However, disadvantages of animal derived hydrogels include lot‐to‐lot variability, an incompletely defined matrix, and species differences which limit applications for translational and in vivo use. Recent progress has systematically developed chemically defined synthetic hydrogels to culture stem cell derived human intestinal and liver organoids that result in organoids that are comparable to those embedded in Matrigel and in some cases can be frozen and thawed (Gjorevski et al., 2016; Kruger et al., 2020; Sorrentino et al., 2020). This new work opens customizable possibilities for clinically relevant studies necessitating defined materials.…”