The origin, biology, and therapeutic potential of facultative adult hepatic progenitor cells

Abstract

The liver plays an essential role in glucose and lipid metabolism, synthesis of plasma proteins, and detoxification of xenobiotics and other toxins. Chronic disease of this important organ is one of the leading causes of death in the United States. Following loss of tissue, liver mass can be restored by two mechanisms. Under normal conditions, or after massive loss of parenchyma by surgical resection, liver mass is maintained by division of hepatocytes. After chronic injury, or when proliferation of hepatocytes is impaired, facultative adult hepatic progenitor cells (HPCs) proliferate and differentiate into hepatocytes and cholangiocytes (biliary epithelial cells). HPCs are attractive candidates for cell transplantation because of their potential contribution to liver regeneration. However, until recently, the lack of highly specific markers has hampered efforts to better understand the origin and physiology of HPCs. Recent advances in cell isolation methods and genetic lineage tracing have enabled investigators to explore multiple aspects of HPC biology. In this review, we describe the potential origins of HPCs, the markers used to detect them, the contribution of HPCs to recovery, and the signaling pathways that regulate their biology. We end with an examination of the therapeutic potential of HPCs and their derivatives.

Keywords: Adult hepatic progenitor cells; Cell therapy; Chronic liver disease; Ductular reaction; Oval cells.

Figure 10.1

Adult hepatic progenitor cells. A subset of cholangiocytes is activated upon injury and gives rise to HPCs that can differentiate into hepatocytes and cholangiocytes.

Figure 10.2

Lineage tracing using the Cre-LoxP approach. Rosa26 promoter is ubiquitously active in mice. However, transcription of YFP reporter is blocked because of the transcriptional stop sequence (Srinivas et al., 2001). The Cre recombinase excises the sequence located between two loxP sites thus allowing for the expression of YFP in a specific cell type.