Open AccessAFP + , ESC‐Derived Cells Engraft and Differentiate into Hepatocytes in Vivo
Author(s) -
Yin Yijun,
Lim Yew Koon,
SaltoTellez Manuel,
Ng Soon Chye,
Lin ChyuanSheng,
Lim SaiKiang
Publication year - 2002
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.20-4-338
Subject(s) - biology , in vivo , microbiology and biotechnology , stem cell , genetics
A major problem in gene therapy and tissue replacement is accessibility of tissue‐specific stem cells. One solution is to isolate tissue‐specific stem cells from differentiating embryonic stem (ES) cells. Here, we show that liver progenitor cells can be purified from differentiated ES cells using alpha‐fetoprotein (AFP) as a marker. By knocking the green fluorescent protein (GFP) gene into the AFP locus of ES cells and differentiating the modified ES cells in vitro, a subpopulation of GFP + and AFP‐expressing cells was generated. When transplanted into partially hepatectomized lacZ ‐positive ROSA26 mice, GFP + cells engrafted and differentiated into lacZ ‐negative and albumin‐positive hepatocytes. Differentiation into hepatocytes also occurred after transplantation of GFP + cells in apolipoprotein‐E‐ (ApoE) or haptoglobin‐deficient mice as demonstrated by the presence of ApoE‐positive hepatocytes and ApoE mRNA in the liver of ApoE‐deficient mice or by haptoglobin in the serum and haptoglobin mRNA in the liver of haptoglobin‐deficient mice. This study describes the first isolation of ES‐cell‐derived liver progenitor cells that are viable mediators of liver‐specific functions in vivo.