Organ Regeneration Based on Developmental Biology

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liver development in concert with endothelial and mesenchymal cells (Fig. 12.3).
Neurons, immune cells, and other cell types may also participate in organ develop-
ment. Accordingly, hepatic differentiation from pluripotent stem cells has been
achieved by recapitulating cellular interactions using added cytokines in cell cul-
tures, resulting in certain degrees of two-dimensional hepatocyte differentiation.
However, there are several issues with these strategies that need to be addressed first
to ensure post-hepatic specification. In particular, current protocols result in liver
tissues with poor differentiation efficiency and immature hepatic function, and clin-
ical applications are hampered by poor engraftment rates (Sasai 2013 ; Collin de
l’Hortet et al. 2016 ; Hannoun et al. 2016 ; Kopp et al. 2016 ; Nicolas et al. 2016 ).

12.2 2D Differentiation of iPSC

The development of iPSC has enabled the use of human pluripotent stem cells
without the ethical issues associated with human embryonic stem cells. Consequent
advances have led to successful differentiation of human pluripotent stem cells

liver bud induction liver bud formation

Maturation &

liver formation

Liver Morphogenesis Adult Liver

Hepatic Specified

Endoderm Cells

Fig. 12.3 Schematic representation of liver development. Sagittal view of liver region during
early development through liver maturation. Foregut endoderm specified to hepatic endodermal
cells (left). The septum transversum mesenchyme and developing heart send out signals to specify
the region of endoderm to become the liver. Hepatic endoderm outgrowth and expand to form the
embryonic liver (middle). Multicellular interactions including hepatocyte, endothelial cells, mes-
enchymal cells, and blood cells promote maturation of the liver (right)

K. Sekine et al.