Int J Stem Cells.  2015 May;8(1):36-47. 10.15283/ijsc.2015.8.1.36.

Cell Sources, Liver Support Systems and Liver Tissue Engineering: Alternatives to Liver Transplantation

• Lee SY
• Kim HJ
• Choi D

• KMID: 2380797
• DOI: http://doi.org/10.15283/ijsc.2015.8.1.36

Abstract

The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells.

Keyword

Hepatocyte; Stem cells; Liver; Bioartificial liver; Liver tissue engineering; Bioprinting

MeSH Terms

Adult
Bioprinting
Extracellular Matrix
Hepatocytes
Humans
Incidence
Liver Diseases
Liver Transplantation*
Liver*
Liver, Artificial
Regenerative Medicine
Stem Cell Research
Stem Cells
Tissue Donors
Tissue Engineering*

Figure

• 

  Fig. 1 Undifferentiated human ES cell derived hepatocyte colony was made by coculture on mitomycin treated NIH 3T3 J2 cells. AFP (A) and albumin (B) were stained with the hepatocytes in the colony. Nuclear staining (C) and merged image (D) showed various differentiation status of human ES derived hepatocytes (magnification; ×200) (54).

• 

  Fig. 2 Typical morphology of the cultured mouse hepatocytes with collagen double gel culture system. Arrows indicate bile canaliculi structure within mouse hepatocytes and cultured hepatocytes showed polygonal shape. Binuclear hepatocytes were present with very clear cytoplasmic margin (magnification; ×200) (63).

• 

  Fig. 3 3D printed hepatic structure was made by 3D bioprinting machine. RFP expressing HepG2 cells were alive in the 3 D printed hepatic structure for over 7 days (magnification; ×200).

Reference

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