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ORGANOTYPIC ECTOCERVICO-VAGINAL TISSUE MODEL CONTAINING DENDRITIC CELLS.

Ayehunie1, S., Cannon1, C.L., Lamore1, S., Kubilus1, J., LaBonte2, J., Pudney3, J., Anderson3, D., Sodroski2, J., and Klausner1, M. 1MatTek Corporation, Ashland, MA 01721, 2Dana Farber Cancer Institute, and 3Brigham and Women's Hospital, Boston, MA, U.S.A.
Abstract

Acquired immunodeficiency syndrome (AIDS) is now the fourth most common cause of death worldwide. In the last 20 years, more than 60 million people have been infected with the virus. By the end of 2001, an estimated 40 million people globally were living with HIV, and the majority of new infections occurred in young adult women through unprotected heterosexual sex. Infection through the ectocervical-vaginal tissue is believed to be the main route for heterosexual transmission of HIV in women. Currently, an appropriate in vitro human tissue model that mimics these squamous epithelial tissues is lacking. In this paper, scientists at Dana Farber Cancer Institute (Boston), Brigham and Women’s Hospital (Boston) and MatTek Corp. describe the development of EpiVaginal™, an in vitro three-dimensional, organotypic ectocervico-vaginal tissue model that contains dendritic cells. Analysis of the tissue showed many of the histological, ultrastructural, and protein expression characteristics of native vaginal/ectocervical tissue. Tissue architectural features include basal, parabasal, glycogenated intermediate, and the superficial cell layers. Initial experimentation showed that HIV virions do not pass freely through the tissue, but they infect cells in the reconstructed ectocervical-vaginal tissue model. The EpiVaginal tissue model could serve as a useful tool to screen new or existing virucides and microbicides for vaginal toxicity and microbicidal efficacy. It should also provide a cost effective means to assess HIV and other sexually transmitted disease related issues while reducing species extrapolation errors related to the use of laboratory animals. Finally, the tissue model will assist researchers in understanding the mechanisms of HIV infection and transmission and in developing prophylactic therapies.

Keywords

ADA, AIDS, Acquired immunodeficiency syndrome, DC, Dendritic cells, Ectocervico, EpiVaginal, Gene expression, HIV, Macrophage tropic, Microbicides, NL4-3, T-cell tropic, Vaginal, Virucides, Yu-2

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