Designing Stem Cell Niche for Liver Development and Regeneration

The liver is known for its robust regenerative capacity. It is thought that liver stem/progenitor cells (LPCs) play an important role during liver regeneration after injury by giving rise to two types of liver epithelial cells: hepatocytes and biliary epithelial cells (cholangiocytes). There is considerable debate in the liver biology community about phenotypic plasticity of liver epithelial cells. It is also becoming increasingly clear that the local microenvironment or niche predisposes LPCs and liver epithelial cells toward certain phenotypes. In this chapter we focus on the mechanisms and "strategies" by which various niche components support LPCs in liver tissue regeneration, including administration of biomaterials or small molecules that target specific aspects of the niche, to stimulate expansion and differentiation of LPCs, or to cause transdifferentiation of adult liver cells. We also illustrate how these mechanisms can be translated into design criteria for liver cell engineers to create biomimetic microenvironments that emulate the native liver niche.