RECONSTRUCTED HUMAN VAGINAL-ECTOCERVICAL TISSUE MODELS.

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 2002, an estimated 42 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 vaginal-ectocervical 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. Here scientists at Dana Farber Cancer Institute (Boston, MA), Brigham and Women’s Hospital (Boston, MA) and MatTek Corp. describe the development of EpiVaginal, an in vitro three-dimensional, organotypic vaginal-ectocervical tissue model that contains dendritic cells. Analysis of EpiVaginal tissues 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 vaginal-ectocervical 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. EpiVaginal tissues 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 EpiVaginal tissue model will assist researchers in understanding the mechanisms of HIV infection and transmission and in developing prophylactic therapies.

AIDS, Acquired immunodeficiency syndrome, Basal, Birbeck granules, DC, Dendritic cells, EpiVaginal, FACS analysis, Gene expression, Glycogenated intermediate, HIV, HIV, HIV infection, HIV transmission, Heterosexual transmission, Lamina propria, Langerhans cells, Macrophage, Microbicidal efficacy, Microbicide, Microbicides, Parabasal, Prophylactic therapies, RNA, RT-PCR, STD, Sexually transmitted disease, Squamous epithelial tissues, T cells, VEC, Vaginal toxicity, Vaginal-ectocervical tissue, Virions, Virucides, Virus

Gamma interferon, Lipopolysaccharide, PMA, Phorbol 12-miristate 13-acetate