Tissue Eng Regen Med.  2016 Dec;13(6):740-749. 10.1007/s13770-016-0094-y.

Functional Comparison of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells as Sources of Hepatocyte-Like Cells

Affiliations
  • 1Department of Surgery, Hanyang University College of Medicine, Seoul, Korea. thicknyh@gmail.com bovie@hanyang.ac.kr
  • 2Department of Anesthesiology and Pain Medicine, Hanyang University College of Medicine, Seoul, Korea.

Abstract

Pluripotent stem cells can differentiate into many cell types including mature hepatocytes, and can be used in the development of new drugs, treatment of diseases, and in basic research. In this study, we established a protocol leading to efficient hepatic differentiation, and compared the capacity to differentiate into the hepatocyte lineage of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Optimal combinations of cytokines and growth factors were added to embryoid bodies produced by both types of cell. Differentiation of the cells was assessed with optical and electron microscopes, and hepatic-specific transcripts and proteins were detected by quantitative reverse transcription polymerase chain reaction and immunocytochemistry, respectively. Both types of embryoid body produced polygonal hepatocyte-like cells accompanied by time-dependent up regulation of genes for α-fetoprotein, albumin (ALB), asialoglycoprotein1, CK8, CK18, CK19, CYP1A2, and CYP3A4, which are expressed in fetal and adult hepatocytes. Both types of cell displayed functions characteristic of mature hepatocytes such as accumulation of glycogen, secretion of ALB, and uptake of indocyanine green. And these cells are transplanted into mouse model. Our findings indicate that hESCs and hiPSCs have similar abilities to differentiate into hepatocyte in vitro using the protocol developed here, and these cells are transplantable into damaged liver.

Keyword

Hepatocyte differentiation; Hepatocyte-like cells; Human embryonic stem cells; Human induced pluripotent stem cells

MeSH Terms

Adult
Animals
Cytochrome P-450 CYP1A2
Cytochrome P-450 CYP3A
Cytokines
Embryoid Bodies
Glycogen
Hepatocytes
Human Embryonic Stem Cells*
Humans*
Immunohistochemistry
In Vitro Techniques
Indocyanine Green
Induced Pluripotent Stem Cells*
Intercellular Signaling Peptides and Proteins
Liver
Mice
Pluripotent Stem Cells
Polymerase Chain Reaction
Reverse Transcription
Up-Regulation
Cytochrome P-450 CYP1A2
Cytochrome P-450 CYP3A
Cytokines
Glycogen
Indocyanine Green
Intercellular Signaling Peptides and Proteins
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