Liver Bioengineering: Promise, Pitfalls, and Hurdles to Overcome

Abstract

Purpose of review: In this review, we discuss the recent advancements in liver bioengineering and cell therapy and future advancements to improve the field towards clinical applications.

Recent findings: 3D printing, hydrogel-based tissue fabrication, and the use of native decellularized liver extracellular matrix as a scaffold are used to develop whole or partial liver substitutes. The current focus is on developing a functional liver graft through achieving a non-leaky endothelium and a fully constructed bile duct. Use of cell therapy as a treatment is less invasive and less costly compared to transplantation, however, lack of readily available cell sources with low or no immunogenicity and contradicting outcomes of clinical trials are yet to be overcome.

Summary: Liver bioengineering is advancing rapidly through the development of in vitro and in vivo tissue and organ models. Although there are major challenges to overcome, through optimization of the current methods and successful integration of induced pluripotent stem cells, the development of readily available, patient-specific liver substitutes can be achieved.

Keywords: Cell therapy; Decellularization; Induced pluripotent stem cells; Liver; Tissue engineering.

Fig. 1

Current applications of liver bioengineering include fabricating partial liver grafts through 3D bioprinting and using hydrogel-based tissues for repairing the lost liver function (a). Recently, the focus has been shifted towards optimizing the decellularization of donor livers rejected for transplantation and their recellularization with iPSC-derived hepatocytes to render them eligible for transplantation (b).

Fig. 2

Transplantation of human hepatic cells (a). Establishment of banked cryopreserved hepatocytes for long-term storage would be of great benefit, allowing on-demand usage for emergency cases (b). iPSCs can be considered as a promising solution since they have advantages such as unlimited self-renewal potential (c). To increase the efficiency of hepatocytes isolation from discarded livers, machine perfusion methods were developed (d). Mesenchymal stem cells (MSC) seem to be a valuable substitute for human primary hepatocytes (e)