Current progress in hepatic tissue regeneration by tissue engineering

Abstract

Liver, as a vital organ, is responsible for a wide range of biological functions to maintain homeostasis and any type of damages to hepatic tissue contributes to disease progression and death. Viral infection, trauma, carcinoma, alcohol misuse and inborn errors of metabolism are common causes of liver diseases are a severe known reason for leading to end-stage liver disease or liver failure. In either way, liver transplantation is the only treatment option which is, however, hampered by the increasing scarcity of organ donor. Over the past years, considerable efforts have been directed toward liver regeneration aiming at developing new approaches and methodologies to enhance the transplantation process. These approaches include producing decellularized scaffolds from the liver organ, 3D bio-printing system, and nano-based 3D scaffolds to simulate the native liver microenvironment. The application of small molecules and micro-RNAs and genetic manipulation in favor of hepatic differentiation of distinct stem cells could also be exploited. All of these strategies will help to facilitate the application of stem cells in human medicine. This article reviews the most recent strategies to generate a high amount of mature hepatocyte-like cells and updates current knowledge on liver regenerative medicine.

Keywords: Hepatic regeneration; Stem cells; Tissue engineering modalities.

Fig. 1

Hepatic tissues from various sources such as human, porcine and rat underwent decellularization using detergents. Repopulation of the decellularized liver scaffold is performed through various routes. Decellularized liver scaffold is chopped to cubes or thin slices then recellularized by microinjection. Whole-organ reseeded by exerting negative pressure suction. Various cell types such as induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs) or liver progenitor cells (LPCs) are used for recellularization

Fig. 2

The impact of various nanostructures on hepatic differentiation. Nanofibers (high surface area, high porosity), nanoparticles (efficiently growth factors delivery) and carbon nanotube (mechanical properties, easily functionalized, aligned as collagen

Fig. 3

Schematic overviews of multi-material 3D bioprinting approach. Sequential 3D bioprinted hepatic lobule-like structures (a). Simultaneous deposited and dual fabricated 3D structures (b)

Fig. 4

A summary of methods used to hepatic differentiation of stem cells using intracellular signaling pathway. DMSO dimethyl sulfoxide, DKK-1 Dikkopf-related protein-1, HNF-3β hepatocyte nuclear factor 3-β, PrP-1 poly-ADP-ribose polymerase-1

Fig. 5

Some of the chemical structures related to small molecules are used commonly for hepatic-like phenotype induction from progenitor cells