Regulated differentiation of stem cells into an artificial 3D liver as a transplantable source

Abstract

End-stage liver disease is one of the leading causes of death around the world. Since insufficient sources of transplantable liver and possible immune rejection severely hinder the wide application of conventional liver transplantation therapy, artificial three-dimensional (3D) liver culture and assembly from stem cells have become a new hope for patients with end-stage liver diseases, such as cirrhosis and liver cancer. However, the induced differentiation of single-layer or 3D-structured hepatocytes from stem cells cannot physiologically support essential liver functions due to the lack of formation of blood vessels, immune regulation, storage of vitamins, and other vital hepatic activities. Thus, there is emerging evidence showing that 3D organogenesis of artificial vascularized liver tissue from combined hepatic cell types derived from differentiated stem cells is practical for the treatment of end-stage liver diseases. The optimization of novel biomaterials, such as decellularized matrices and natural macromolecules, also strongly supports the organogenesis of 3D tissue with the desired complex structure. This review summarizes new research updates on novel differentiation protocols of stem cell-derived major hepatic cell types and the application of new supportive biomaterials. Future biological and clinical challenges of this concept are also discussed.

Co-culture of liver parenchymal cells with non-parenchymal cells under 2D and 3D culture systems; a review paper

“…Co-culture of hepatocytes with supporting cells enhances the maturation and maintenance of hepatocytes. Supporting cells can be derived from matched or non-matched hepatocyte donors [70] and pluripotent stem cells [71]. The cell ratio of PC and NPC is very important.…”

Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine

“…In one successful example, splenic dECM scaffolds have shown promising results for bioengineering the liver and pancreas. However, further studies should be done on this idea before translation into the clinic [230,231].…”