Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance.

In order to progress beyond currently available medical devices and implants, the concept of tissue engineering has moved into the centre of biomedical research worldwide. The aim of this approach is not to replace damaged tissue with an implant or device but rather to prompt the patient's own tissue to enact a regenerative response by using a tissue-engineered construct to assemble new functional and healthy tissue. More recently, it has been suggested that the combination of Synthetic Biology and translational tissue-engineering techniques could enhance the field of personalized medicine, not only from a regenerative medicine perspective, but also to provide frontier technologies for building and transforming the research landscape in the field of in vitro and in vivo disease models.

Transient neonatal estrogen exposure to estrogen-deficient mice (aromatase knockout) reduces prostate weight and induces inflammation in late life.

Exposure of newborn male mice to estrogens is associated with age-related changes in prostate size and induction of epithelial hyperplasia and dysplasia. Whether these changes directly result from systemic estrogen administration or indirect effects of estrogens on systemic testosterone levels is unclear. We have addressed this question using aromatase-knockout (ArKO) mice that are estrogen-deficient during their lifespan but have elevated androgen levels and develop prostate enlargement and hyperplasia (McPherson SJ, Wang H, Jones ME, Pedersen J, Iismaa TP, Wreford N, Simpson ER, Risbridger GP: Endocrinology 2001, 142:2458-2467).

Direct response of the murine prostate gland and seminal vesicles to estradiol.

In the prostate, testosterone action depends on conversion to bioactive metabolites dihydrotestosterone and 17beta-estradiol (E2) via the 5alpha-reductase and aromatase enzymes, respectively. Exogenous estrogen inhibits prostate growth by indirect effects caused by suppression of pituitary gonadotropins and testicular testosterone output, but direct effects are less well known. Direct effects of estrogens were evaluated using the hypogonadal (hpg) mouse model, which has postnatal deficiency in gonadotropins and testosterone but remains hormone sensitive.