The quest for liver progenitor cells: A practical point of view

Abstract

Many chronic liver diseases can lead to hepatic dysfunction with organ failure. At present, orthotopic liver transplantation represents the benchmark therapy of terminal liver disease. However this practice is limited by shortage of donor grafts, the need for lifelong immunosuppression and very demanding state-of-the-art surgery. For this reason, new therapies have been developed to restore liver function, primarily in the form of hepatocyte transplantation and artificial liver support devices. While already offered in very specialized centers, both of these modalities still remain experimental. Recently, liver progenitor cells have shown great promise for cell therapy, and consequently they have attracted a lot of attention as an alternative or supportive tool for liver transplantation. These liver progenitor cells are quiescent in the healthy liver and become activated in certain liver diseases in which the regenerative capacity of mature hepatocytes and/or cholangiocytes is impaired. Although reports describing liver progenitor cells are numerous, they have not led to a consensus on the identity of the liver progenitor cell. In this review, we will discuss some of the characteristics of these cells and the different ways that have been used to obtain these from rodents. We will also highlight the challenges that researchers are facing in their quest to identify and use liver progenitor cells.

Podoplanin discriminates distinct stromal cell populations and a novel progenitor subset in the liver

“…While hepatocytes provide the major source for liver regeneration, liver damage is accompanied by extensive progenitor cell expansion (7). These cells termed oval cells are quiescent at steady state and emerge in the portal or periportal area during injury (7,27,30,38,49).…”

“…While hepatocytes provide the major source for liver regeneration, liver damage is accompanied by extensive progenitor cell expansion (7). These cells termed oval cells are quiescent at steady state and emerge in the portal or periportal area during injury (7,27,30,38,49). They exhibit bipotential differentiation capacity and are able to give rise to both hepatocytes and cholangiocytes in vitro (7,9,38,39) and in vivo (39,42).…”

“…These cells termed oval cells are quiescent at steady state and emerge in the portal or periportal area during injury (7,27,30,38,49). They exhibit bipotential differentiation capacity and are able to give rise to both hepatocytes and cholangiocytes in vitro (7,9,38,39) and in vivo (39,42). However, genetic tracing of Foxl1 ϩ (39) and Sox9 ϩ (42) oval cells indicated that these cells do not contribute significantly to hepatocyte regeneration in vivo, demonstrating an undetermined role of progenitor cell expansion during liver injury.…”

“…Many of these markers are corresponding to hematopetic stem cells or mesenchymal progenitor cells suggesting a heterogeneous population of precursors identified as oval cells within the liver. Despite of extensive studies, using primarily histology and PCR analyses, the characteristic marker combinations and molecular signatures remain elusive (7).…”

Transplantation of Cryopreserved Fetal Liver Cells Seeded Into Macroporous Alginate-Gelatin Scaffolds in Rats With Liver Failure

“…фетальной печени по сравнению со зрелыми гепа-тоцитами является высокая пролиферативная ак-тивность первых из них [7] и меньшая чувствитель-ность к факторам криоконсервирования [2,8], что позволяет создавать запас криоконсервированных клеток, пригодных для трансплантации.…”