Signaling molecules orchestrating liver regenerative medicine

The liver is in charge of more than 500 functions in the human body, which any damage and failure to the liver can significantly compromise human life. Numerous studies are being carried out in regenerative medicine, as a potential driving force, toward alleviating the need for liver donors and fabrication of a 3D-engineered transplantable hepatic tissue. Liver tissue engineering brings three main factors of cells, extracellular matrix (ECM), and signaling molecules together, while each of these three factors tries to mimic the physiological state of the tissue to direct tissue regeneration. Signaling molecules play a crucial role in directing tissue fabrication in liver tissue engineering. When mimicking the natural in vivo process of regeneration, it is tightly associated with three main phases of differentiation, proliferation (progression), and tissue maturation through vascularization while directing each of these phases is highly regulated by the specific signaling molecules. The understanding of how these signaling molecules guide the dynamic behavior of regeneration would be a tool for further tailoring of bioengineered systems to help the liver regeneration with many cellular, molecular, and tissue-level functions. Hence, the signaling molecules come to aid all these phases for further improvements toward the clinical use of liver tissue engineering as the goal.