AFP(+), ESC-derived cells engraft and differentiate into hepatocytes in vivo

Y. Yin, Y.K. Lim, Manuel Salto-Tellez, S.C. Ng, C.S. Lin, S.K. Lim

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)338-346
Number of pages9
JournalStem Cells
Volume20
Issue number4
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Cell Biology

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