Cell-Based Regeneration and Treatment of Liver Diseases

Abstract

The liver, in combination with a functional biliary system, is responsible for maintaining a great number of vital body functions. However, acute and chronic liver diseases may lead to irreversible liver damage and, ultimately, liver failure. At the moment, the best curative option for patients suffering from end-stage liver disease is liver transplantation. However, the number of donor livers required by far surpasses the supply, leading to a significant organ shortage. Cellular therapies play an increasing role in the restoration of organ function and can be integrated into organ transplantation protocols. Different types and sources of stem cells are considered for this purpose, but highly specific immune cells are also the focus of attention when developing individualized therapies. In-depth knowledge of the underlying mechanisms governing cell differentiation and engraftment is crucial for clinical implementation. Additionally, novel technologies such as ex vivo machine perfusion and recent developments in tissue engineering may hold promising potential for the implementation of cell-based therapies to restore proper organ function.

Keywords: cell therapy; immunotherapy; liver; regeneration; stem cells.

Figure 2

Different sources of stem cells and their mechanism of differentiation for cell-based therapies. ESCs (A) are isolated from the early blastocyst [61]. The sources of HSCs (B) and MSCs (C) include placenta, umbilical cord, bone marrow, and peripheral blood; for MSC, additionally, dental pulp, muscle, and adipose tissue can be utilized [60,83]. iPSCs (D) are derived from somatic cells by a reprogramming step. Triggered by different transcription and growth factors, all of them can be differentiated into hepatocytes.

Figure 1

Histoarchitecture of the liver. The portal triad is composed of the bile duct (A), the portal vein (B), and the hepatic artery (C) [8]. The blood flows from the portal vein and hepatic artery through the sinusoids (E) towards the central vein (F), surrounded by fenestrated LSECs. Lymphocytes and KCs reside intravascular, whereas SCs are found in the space of Disse (D) [1]. BECs line the bile duct, where they modify the bile produced by hepatocytes. The junctional region between the bile duct and hepatocytes, known as the canal of Hering (G), harbors bipotential BECs [12].