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Stem Cells 2003;21:449-458 www.StemCells.com
© 2003 AlphaMed Press

Hepatic Progenitor Cell Lines from Allyl Alcohol-Treated Adult Rats Are Derived from {gamma}-Irradiated Mouse STO Cells

Mingjun Zhanga,c, Stewart Sellc, Hyam L. Lefferta,b

a Department of Pharmacology and
b Center for Molecular Genetics, University of California, San Diego, La Jolla, California, USA
c Division of Experimental Pathology, Albany Medical College, Albany, New York, USA

Key Words. STO cell feeder layers • Radiation artifacts

Hyam L. Leffert, M.D., Department of Pharmacology and Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093-0636, USA. Telephone: 858-534-2354; Fax: 858-534-6833; e-mail: hleffert{at}ucsd.edu website: http://medicine.ucsd.edu/pharmaco/hlleffert.html

In attempts to recharacterize several markers of putative rat liver progenitor cells, single-stage reverse transcription-polymerase chain reaction (RT-PCR) analyses failed to confirm the reported immunochemical detection of albumin, {alpha}1-fetoprotein, and cytochrome P450-1A2 in the clonal line, 3(8)#21, and the cloned derivative, 3(8)#21-EGFP (enhanced green fluorescent protein). Undetectable expression occurred whether or not both lines were cultured on or off feeder layers of {gamma}-irradiated mouse embryonic STO (SIM [Sandoz inbred Swiss mouse] thioguanine-resistant ouabain-resistant) cells. PCR amplification of liver progenitor cell chromosomal (rat and mouse Pigr, rat INS1, mouse INS2) and mitochondrial (rat and mouse COX1) genes revealed only mouse sequences. Further analyses of rat and mouse COX1 sequences in cells from untampered storage vials of all 11 reported liver progenitor cell lines and strains revealed only mouse sequences. In addition, uniquely similar metaphase spreads were observed in STO, 3(8)#21, and 3(8)#21-EGFP cells. The combined results suggest that the previously reported "rat" liver progenitor cell lines were most likely generated during early derivation in cell culture from {gamma}-radiation-resistant or ineffectively irradiated mouse STO cells used as the feeder layers. These findings reveal new types of artifacts encountered in cocultures of tissue progenitor cells and feeder layer cell lines, and they sound a cautionary note: phenotypic and genotypic properties of feeder layers should be well-characterized before and during coculture with newly derived stem cells and clonal derivatives.




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M. Zhang, B. Joseph, S. Gupta, I. Guest, M. Xu, S. Sell, K.-H. Son, K. S. Koch, and H. L. Leffert
Embryonic Mouse STO Cell-Derived Xenografts Express Hepatocytic Functions in the Livers of Nonimmunosuppressed Adult Rats
Stem Cells, February 1, 2005; 23(2): 186 - 199.
[Abstract] [Full Text] [PDF]


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