Pluripotent plasticity of stem cells and liver repopulation

Abstract

Different types of stem cells have a role in liver regeneration or fibrous repair during and after several liver diseases. Otherwise, the origin of hepatic and/or extra-hepatic stem cells in reactive liver repopulation is under controversy. The ability of the human body to self-repair and replace the cells and tissues of some organs is often evident. It has been estimated that complete renewal of liver tissue takes place in about a year. Replacement of lost liver tissues is accomplished by proliferation of mature hepatocytes, hepatic oval stem cells differentiation, and sinusoidal cells as support. Hepatic oval cells display a distinct phenotype and have been shown to be a bipotential progenitor of two types of epithelial cells found in the liver, hepatocytes, and bile ductular cells. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy, and acute or chronic hepatopaties. In the future, pluripotent plasticity of stem cells will open a variety of clinical application strategies for the treatment of tissue injuries, degenerated organs. The promise of liver stem cells lie in their potential to provide a continuous and readily available source of liver cells that can be used for gene therapy, cell transplant, bio-artificial liver-assisted devices, drug toxicology testing, and use as an in vitro model to understand the developmental biology of the liver.

In vitro differentiated hepatic oval‐like cells enhance hepatic regeneration in CCl4‐induced hepatic injury

“…Oval cells are the hepatic progenitor cells and express markers of hepatic origin (Gennero et al, ). BMSCs after 14 days of preconditioning with growth factors started expressing oval cells‐specific markers as evidenced by immunocytochemical analysis.…”

“…OCs are bipotent and are able to give rise to both cholangiocytes and hepatocytes. These cells co‐express biliary and hepatocyte markers such as cytokeratin‐19 (CK19), AFP, and ALB and also mesenchymal stem cell (MSC) markers; c‐kit and Thy‐1 (CD90) (Gennero et al, ; Jackson et al, ). Oval cells are there in limited number in normal adult liver so their isolation is not a practical therapeutic option in human liver diseases (Schmelzer et al, ; Bird et al, ).…”

Therapeutic potential of mesenchymal stem cells overexpressing human forkhead box A2 gene in the regeneration of damaged liver tissues

“…Recent rapid developments in stem cell biology have made its use possible in the treatment of several types of diseases 25,26 . In this context, adult stem cells have shown the capacity for regeneration of damaged tissues or organs, including the liver 27,28 . Studies have demonstrated that bone marrow‐derived MSC migrate into the damaged liver and contribute to overcoming liver dysfunction 29,30 .…”

BMPS and Liver: More Questions than Answers

“…are not yet fully understood [84,85]. Given the multifunctional role assigned to BMP signaling during early liver development, including hepatic specification and liver morphogenesis, a potential role for BMP in oval cell activation, expansion and differentiation should be considered.…”