Regenerative medicine in the testis: Defining and manipulating the Leydig stem cell niche through gene therapy to promote lifelong male health

The increasing proportion of older men in the UK population brings with it an increase in age-related conditions, such as cardiovascular disease, obesity, loss of bone density, muscle strength, libido and erectile function, and these are often associated with an age-related reduction in androgen (testosterone) levels. The most obvious changes in men are a reduction in testicular Leydig cell (LC) numbers with age and reduced testosterone production per LC. However, the underlying cause for these failures remains unclear. If LC numbers could be maintained in older men this might maintain testosterone concentrations for that individual without the concerns associated with exogenous steroid administration (e.g. overstimulation of prostate tissue). This project aims to understand how quiescent LC stem cells are activated, and develop methodologies to control proliferation and function of LCs, such that ectopically induced LC regeneration can be explored as a future clinical therapeutic for androgen-related conditions..

The project aims to investigate LC renewal using three complementary approaches (1) regeneration of new LCs from the resident testicular stem cell population in transgenic mice, (2) replacement with new LCs developed from stem cells in vitro, (3) correction/replacement of the LC population through viral-mediated gene therapy.