Progenitor Cells in Liver Development, Regeneration and Repair

Abstract

During organogenesis, the liver develops from the foregut endoderm and grows into the adjacent septum transversum resulting in the formation of the liver bud. Growth factors released from the septum transversum and the cardiac mesenchyme induce endodermal differentiation and proliferation, thus, forming the primordial liver and extrahepatic biliary structures. Endodermal precursor cells within the liver bud comprise bi-potential liver progenitor cells called hepatoblasts, which differentiates into hepatocytes and cholangiocytes. While the postnatal liver has remarkable capacity to regenerate via the proliferation of mature hepatocytes, this compensatory mechanism may be overwhelmed during states of chronic injury. Under these conditions, resident stem/progenitor cells proliferate to replace lost liver parenchyma. Significant progress has been made recently in elucidating the role of various signaling pathways and progenitor cells in liver development and regeneration. In this review, we summarize our recent understanding of progenitor cells in liver development, regeneration, and repair.

Specific Markers for Hepatic Progenitor Cells

“…The cells serve as hepatic progenitor cells in adult liver and display a highly proliferative activity during chronic liver injury. They were found both in rodent and human at Canal of Hering alongside the portal triad (Mavila et al, 2014;Hu et al, 2007). Proliferation of oval cells starts after liver injury or when hepatocyte function is impaired, as displayed in animal model induced with 2-Acetylaminofluore Followed with Partial Hepatectomy (2-AAF/PH).…”

“…EpCAM, OV6, Prominin 1, CD49f and A6, with AFP positive or negative. In this condition, however, similar to the maturation and differentiation process, it has not been agreed whether there are any reprogramming of hepatocytes or not (Mavila et al, 2014). In liver malignancy and chronic liver disease, HPCs presented as Ductular Reactions (DR).…”

“…The uniqueness of liver regeneration is that the responsible cells to repair the liver are differentiated cell, i.e., hepatocytes and cholangiocytes, despite of its low of mitotic rate (Hu et al, 2007;Marongiu et al, 2014). Nevertheless, the responsibility to restore liver mass is taken over by Hepatic Progenitor Cells (HPCs) under certain condition that deteriorates hepatocytes, such as in chronic liver pathologic condition or severe loss of liver mass (70% hepatectomy) (Mavila et al, 2014;Fausto, 2004). The HPCs are assumed to be an embryonic residual from embryonic hepatoblast that remain in adult liver; even though, the origin and relationship between them have not yet been clearly understood.…”

“…Oval cells are bi-potent as they can differentiate into hepatocytes (positive for Albumin and positive or negative for AFP) and cholangiocytes (positive for CK19), characteristics that are similar to embryonic hepatoblast (Zhou et al, 2007;Mavila et al, 2014;Hu et al, 2007;Romano et al, 2015). The cells serve as hepatic progenitor cells in adult liver and display a highly proliferative activity during chronic liver injury.…”