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ToxSci Advance Access published online on September 7, 2006
Toxicological Sciences, 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
Received May 28, 2006
Accepted August 28, 2006

In Vitro Toxicology

The Effects of Anticholinergic Insecticides on Human Mesenchymal Stem Cells

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

1 Biomedical Tissue Research Group, Department of Biology, University of York, Heslington, York, YO10 5YW, UK
2 Dept. Oral Biology, Dept. Psychiatry, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, Faculty of Medicine, University of Szeged, Szeged, Hungary

* To whom correspondence should be addressed.
Paul G. Genever, E-mail: pg5{at}york.ac.uk


  Abstract

Mesenchymal stem cells (MSCs) are located primarily in the bone marrow and are characterised by their capacity to differentiate into mesenchymal lineages such as bone, fat and cartilage in response to appropriate signals. Several signalling mechanisms act to control MSC survival, proliferation and differentiation and failure or disruption of these signalling 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 signalling 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 non-nervous 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.

Keywords: Acetylcholine; Acetylcholinesterase; Carbofuran; Chlorpyrifos; Mesenchymal Stem Cell; Osteogenesis.
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