Stem cells for liver repopulation

Abstract

Purpose of review: The capacity of the liver to regenerate and maintain a constant size despite injury is unique. However, the exact mechanisms are not completely clear. Cell transplantation has been proposed as an alternative treatment of liver diseases. Recent progress has been reported on the generation of stem/progenitor cells that may differentiate toward the hepatic lineage. However, it is currently difficult to determine which of the stem/progenitor cell populations are the best for therapy of a given disease.

Recent findings: The limited access to donor human hepatocytes has led to a great interest in the generation of hepatocyte-like cells. Several potential cell sources have been identified. However, general standardization of the methods to evaluate these cells is particularly important for the promise of stem/progenitor-derived hepatocyte-based therapies. Moreover, innovations aimed at improving hepatocyte delivery, survival, and engraftment have recently opened the field of organ engineering that may improve liver repopulation.

Summary: Here we review current evidence reported from the perspective of potential clinical applications of different hepatic cell sources with repopulation capacities and the future perspectives and tools that can facilitate the translation of laboratory work into clinical success.

Fig 1. Cell-based therapies for liver repopulation

Cells with adult liver repopulating potential are transplanted via portal vein, donor hepatocytes translocates to the liver and accumulates in the hepatic sinusoids. Passage of hepatocytes into the space of Disse requires retraction of the sinusoidal endothelial cells. Shortly after entering the Space of Disse there is a transient disruption of the gap junction and tight junction between adjacent hepatocytes in the vicinity of the transplanted hepatocytes. The transplanted cells then insert themselves between host hepatocytes, with subsequent regeneration of the bile canaliculi and gap junctions.