Because the procedure is less invasive than orthotopic liver transplantation and can be performed repeatedly, it could also be used in patients who are severely ill and unable to tolerate organ transplantation. Some studies have demonstrated its efficacy, experimentally and clinically.11 selleck bio However, poor engraftment of transplanted hepatocytes remains a major barrier to the successful expansion of hepatocyte transplantation therapy.12,13 Tissue engineering is an attractive approach to improvement of cell engraftment. Enhancing cell-cell contact and providing nonimmunogenic matrices before transplantation has been shown to improve cell engraftment in animal models.14 Furthermore, tissue-engineered products, such as skin substitutes and cartilage replacement, have already helped thousands of patients15,16 and other artificial tissues, such as bladder, cornea, bronchial tubes and blood vessels, are in clinical trials.
15,16 Thus, liver tissue engineering is considered a potentially valuable new therapeutic modality for liver disease. Liver Tissue Engineering for Reconstructing 3D Liver Tissues In a common approach to liver tissue engineering, parenchymal cells alone and/or a mixed population of parenchymal and non-parenchymal cells (NPCs) are combined with various forms of three-dimensional (3D) scaffolds and appropriate signaling molecules, such as cytokines or growth factors, that facilitate cell growth, organization, and differentiation. These processes can be classified into two categories. The first involves suspending hepatocytes in extracellular matrix (ECM) components (Fig.
1A). Hepatocytes grown on collagen-coated polystyrene beads in roller bottle cultures with NPCs were allowed to form cell clusters and were implanted in Matrigel, self-organizing into hepatic plate-like architectures three-dimensionally.17 Fetal liver progenitor cells were co-cultured in 3D fibrin gel with endothelial cells, resulting in the formation of vascular structures by the endothelial cells and increased proliferation and function of liver progenitor cells.18 Hepatocytes were transplanted into the subcutaneous space, where new vascular network formation was induced in advance by transplanting a polyethylene terephthalate mesh device coated with poly(vinylalcohol) that allowed for the gradual release of basic fibroblast growth factor (bFGF), resulting in persistent survival for up to 120 d.
19 Photo-polymerization of a hepatocyte-suspended poly(ethylene glycol) (PEG)-based hydrogel has been developed for the reconstruction of 3D liver architectures.20 Hepatocytes suspended in a pre-polymer GSK-3 solution were photo-immobilized locally within a 3D cell-hydrogel network, thus forming a functional 3D liver construct with complex internal architectures. Figure 1. Liver tissue engineering approaches. (A) Cells are suspended in extracellular matrix (ECM) components and then poured into a mold to let the suspensions being polymerized.