Wishing the WISH cells were pure

Abstract

To the Editors: We read with interest the article of Millar et al1 indicating that insulin-like growth factor (IGF)-2 and relaxin cause the proliferation of “human amnion” WISH cells. The authors conclude that relaxin is a growth factor for fetal membranes, likely acting through transcriptional up-regulation of IGF-2. Despite the convincing results in cell culture, issues of WISH cell contamination and interpretation of their data from the human fetal membrane study result in caution in their conclusion. The authors note appropriately that WISH cells are not primary amniotic epithelial cells because they have characteristics of HeLa cells. This potentially understates the degree of contamination of the WISH cell line with HeLa cells, as Kniss et al2 have demonstrated by polymerase chain reaction HLA typing that WISH cells are identical to HeLa cells, indicating that the WISH cells, as currently exist, are not human amnion epithelial cells. This issue is similarly a concern in our recent finding of cyclic adenosine monophosphate up-regulation of aquaporin 8 in the WISH cell line.3 Millar et al demonstrated that increased relaxin gene expression in human amnion is associated with both increased amnion size and macrosomic infants. However, they suggest a causative role rather than the equally likely potential of a common mediator of fetal/amnion growth and relaxin gene expression. The contamination of the WISH cell line with HeLa cells and the lack of mechanistic evidence in the human data raise caution to the conclusion that relaxin functions as an in vivo growth factor of human fetal membranes. Clearly, relaxin stimulates cell proliferation in the in vitro “WISH” cell culture. However, the true role of relaxin in proliferation of human amnion epithelium will await studies, perhaps in primary human amnion cell culture, because there is no established and uncontaminated human amnion cell line available.