A Review of Stem Cell Technology Targeting Hepatocyte Growth as an Alternative to Organ Transplantation.

Currently, the only feasible option for patients with progressive and/or end-stage organ degeneration is to undergo transplantation. Due to the growing unmatched demand of available organ donors and, as a consequence, the continuous growth of patients' waiting lists, the development of new tissue engineering technologies is a relevant need. In this chapter, we will focus on the liver as a model organ to discuss contemporary tissue engineering strategies. Induced pluripotent cells are an attractive alternative to serve as a cell source for tissue engineering applications due to their pluripotency, the potentiality to generate autologous transplantation, and for their high proliferation rate. Among the main liver tissue engineering technologies, 3D bioprinting, hepatic organoids, and decellularization/recellularization of biological matrixes have grown much attention as alternatives to derive functional liver grafts. Thus, this chapter will discuss how recent publications have demonstrated the use of induced pluripotent cells in the development of the aforementioned technologies. Bioprinting is an additive manufacturing biofabrication process where cells are dispersed within a matrix formulation (i.e., bioink) and extruded in a modified 3D-printer. Polymers within bioink can be cross-linked to increase stiffness. Hepatic spheroids showed greater viability and liver function, due to preserved epithelial phenotype over time. Organoid is multi-lineage tissue constructs derived from a stem cell that recapitulates the early stages of organogenesis. The influence of cellular composition of non-parenchymal cells using induced pluripotent-derived cells or primary adult cells for hepatic organoid formation was recently tested. Decellularization is a process where harvested tissues or organs are washed with a detergent-based solution, to lyse and remove all cellular components. The final product is an extracellular scaffold with preserved tissue vasculature and ultra-structure, which can be used for subsequent recellularization with recipient cells. This chapter sheds light on recent works on the use of induced pluripotent-derived cells for liver tissue engineering approaches and on how such technologies could potentially generate therapeutic alternatives for patients on waiting lists for liver transplantation.