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Abstract
Grant Number: 1R43HD056620-01 Project Title: Human Sertoli Cell Model for Study of Male Reproductive Function and Toxicity
PI Information: Name Title JOHN, CONSTANCE M. connie@mandalmed.com PRESIDENT Abstract: DESCRIPTION (provided by applicant): The overall goal of the Phase I research is to develop a three-dimensional model of the blood-testis barrier (BTB) consisting of primary human Sertoli cells cultured on permeable membrane supports. The human Sertoli cells have been isolated from normal human testis tissue by MandalMed scientists using a novel patent-pending methodology. To our knowledge, due to difficulty in their isolation human Sertoli cells have never been readily available before for in vitro studies. Applications of the product include studies of the distribution and toxicology of drugs and industrial chemicals, infertility research, development of male contraceptive agents, and eventually for creation of a model of human spermatogenesis. There is a great need for more accurate, less costly and time- consuming methods of assessing effects on drug distribution in the testis, reproductive function and toxicity. Three Specific Aims have been identified for the Phase I research as described below. I. Develop a transwell three-dimensional culture system for primary human Sertoli cells as a model of the blood-testis barrier (BTB). II. Assess the ability of model compounds to affect permeability of the model BTB. III. Assess the toxicity of compounds for the model BTB. Areas of focus that are envisioned for Phase II are identification of genetic or proteomic markers for human Sertoli cell function, including the formation or disruption of junctions, transporters, immunomodulation, comparisons with animal studies of distribution of drugs for the testis, male reproductive toxicity, and the standardization as a method for quantifying human BTB permeability and Sertoli cell toxicity. In Phase II we will develop more complex, multicellular model systems. The overall goal of the Phase I research is to develop a three-dimensional model of the blood-testis barrier (BTB) consisting of primary human Sertoli cells cultured on permeable membrane supports. Applications of the product include studies of the distribution and toxicology of drugs and industrial chemicals, infertility research, development of male contraceptive agents, and eventually for creation of a model of human spermatogenesis. There is a great need for more accurate, less costly and time- consuming methods of assessing effects on reproductive function and toxicity.
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Institution: MANDALMED, INC. 665 3rd Street SAN FRANCISCO, CA 941071953 Fiscal Year: 2007 Department: Project Start: 14-AUG-2007 Project End: 13-JUL-2008 ICD: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT IRG: ZRG1