Human stem Leydig cells: A possible source for cell therapy in hypogonadism?

Hypogonadism, a clinical condition due to low testosterone levels is associated with increased visceral fat, decreased muscle mass, erectile dysfunction, reduced libido, depression and changes in mood. Hypogonadism might occur after testicular sperm extraction, although its exact effect on testosterone levels and consequently the risk on hypogonadism is still unclear. Other causes of hypogonadism can be orchitis, disorders of sexual development, mutations in the luteinizing hormone receptor, medication or graft-versus-host disease. To treat hypogonadism, testosterone replacement therapy is currently a common intervention to increase testosterone levels and with that to alleviate symptoms. A completely different avenue to address hypogonadism is by physiologically restoring testosterone levels by cell therapy. Cell therapy to treat hypogonadism is however currently unavailable, largely because the adequate cell type to use for cell therapy is yet to be identified. An interesting candidate cell type in this respect is the stem Leydig cell, which has the capacity to differentiate into testosterone producing adult Leydig cells. How to identify and properly isolate these cells from the human testis is at present unknown.
In this thesis, we aimed at clarifying the risk of hypogonadism after testicular sperm extraction in men with azoospermia. We did this by performing a systemic literature review and a cohort study. In addition, we investigated the expression of multiple proteins in human testicular interstitial cells, and their potential to be used as markers for the isolation of human stem Leydig cells as a first prerequisite step for future cell therapy.