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ToxSci Advance Access originally published online on September 7, 2006
Toxicological Sciences 2006 94(2):342-350; doi:10.1093/toxsci/kfl101
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The Effects of Anticholinergic Insecticides on Human Mesenchymal Stem Cells

Martin J. Hoogduijn*,2, Zoltan Rakonczay{dagger} and Paul G. Genever*,1

* Biomedical Tissue Research Group, Department of Biology, University of York, Heslington, York, YO10 5YW, United Kingdom {dagger} Department Oral Biology and Department of Psychiatry, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, Faculty of Medicine, University of Szeged, Szeged, Hungary, 3000CA

Received May 28, 2006; accepted August 28, 2006

Mesenchymal stem cells (MSCs) are located primarily in the bone marrow and are characterized by their capacity to differentiate into mesenchymal lineages such as bone, fat, and cartilage in response to appropriate signals. Several signaling mechanisms act to control MSC survival, proliferation, and differentiation, and failure or disruption of these signaling pathways can lead to degenerative disease or neoplasia. Organophosphate (OP) and carbamate pesticides, which are used in large amounts in agriculture to control insects, are designed to disrupt acetylcholine signaling by inhibiting the enzyme acetylcholinesterase (AChE). Effects of OP and carbamate pesticides on the human central nervous system have been well documented. However, AChE is broadly distributed, and the effects of anticholinergic insecticides on nonnervous tissue have received little attention. In the present study we found that human MSCs express AChE, which makes these cells potential targets for AChE inhibiting agents. We therefore examined the effects of an OP pesticide, chlorpyrifos, and a carbamate, carbofuran, on MSC characteristics. It was found that micromolar concentrations of these anticholinergic insecticides had no effect on MSC survival or proliferation but limited MSC differentiation capacity by inhibiting osteogenic differentiation. These results demonstrate that exposure to micromolar concentrations of OP and carbamate pesticides may affect tissue turnover and pathophysiology by interfering with MSC regulation.

Key Words: acetylcholine; acetylcholinesterase; carbofuran; chlorpyrifos; mesenchymal stem cell; osteogenesis.


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