Grant: Project Grant

The production of sperm in vitro, either from stem cells or from immature germ cells, has been called the 'holy grail' of reproductive medicine and, so far, has only been successful in mice and rats. Testis organoids are 'miniature testes' that mimic testis function in vitro and can allow us to model human spermatogenesis, to study testes development, male fertility, and contraception, and to reduce the need for animal testing for drugs and toxicants. Taking advantage of our expertise in stem cells, male reproduction, and biomedical engineering, we will create and validate an innovative organoid system using induced pluripotent stem cells. Initially, we will use pigs as models for easy access to testes and stem cells and their similarity to humans. What we learn from pigs will be applied to model human spermatogenesis in vitro. We will test a novel engineered fluidics method to keep these organoids alive and functioning over time, and to study how to efficiently get germ cells from stem cells in this environment and how to form testicular organoids entirely from stem cells. Our goal is to create a unique platform to help understand how testes develop and make sperm. This work will be the basis for clinically preserving and restoring male fertility or understanding why some men struggle with infertility. Ultimately, this research could help childhood cancer survivors recover fertility after treatment or transgender individuals have their own genetic children, and eventually allow patient-specific studies to treat male infertility. This stem cell-derived platform can also serve as a New Alternative Method to reduce the need for animals when testing the effects of drugs and toxicants on human testis development and sperm production.