AFP(+), ESC-derived cells engraft and differentiate into hepatocytes in vivo.
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.
Yin
Yijun
Y
Genome Institute of Singapore, The National University of Singapore, Singapore.
Lim
Yew Koon
YK
Salto-Tellez
Manuel
M
Ng
Soon Chye
SC
Lin
Chyuan-Sheng
CS
Lim
Sai-Kiang
SK
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D002469:Cell Separation / Q000379:methods* / Q000639:trends; D002478:Cells, Cultured; D005260:Female; D006085:Graft Survival / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D039901:Totipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism*
D001057:Apolipoproteins E; D015415:Biomarkers; D000509:alpha-Fetoproteins