Brief Summary

The identification of new therapeutic targets or biomarkers is a specific hallmark in laboratory medicine, the recent advancements in biotechnology pointed out that services offered by the laboratory to the medical community should also include the development and production of cell-based and tissue-engineering applications for pathologies with limited treatment options and for rare diseases. The “bench to bedside” process, should lead the Laboratory Medicine community to encourage specific protocols for the development of advanced therapies and their faster application into clinical practice.

 

Abstract

“Perspectives on women’s health care: novel approaches for rare diseases, aging and cancer”.

Cinzia Marchese, Francesca Megiorni, Simona Ceccarelli

Our group focused its attention on issues related to women’s health care. In this field, we developed a revolutionary approach to treat patients affected by Mayer-von-Rokitansky-Kuster-Hauser (MRKH) syndrome, a rare disease that occurs in 1/4500 females and is characterized by vaginal agenesis. The surgical reconstruction of a neovagina is the most common treatment option in these women. Between 2006 and 2016, our laboratory and clinical team has followed and treated a consecutive series of 39 women with MRKH, performing vaginoplasty with a modified Abbè-Mclndoe technique using autologous in vitro cultured vaginal tissue, obtained from a full-thickness mucosal biopsy of the vaginal vestibule. This tissue-engineered-medicine-based approach is characterized by the fast availability of the biological product (20-30 days), the minimally invasive procedure (with no abdominal approach) and the final result ensuring an anatomically and functionally normal vagina, since it is elastic and lubricated thanks to the presence of interspersed cells important for the spontaneous mucus production.

Another important topic in the context of women’s health care is represented by menopause, characterized by estrogen deficiency, which in turn might cause systemic symptoms, including night sweats, hot flashes, mood fluctuations and cognitive changes. Estrogen loss also induce vaginal symptoms (dysuria, pain, mucosal atrophy and vaginal drying) that represent a significant health concern for the female population. Vaginal symptoms can occur also in premenopausal women following local treatments for endometrial cancer, such as vaginal brachytherapy. Treatments based on local estrogen administration have been questioned as topic estrogens can reach the bloodstream, thus leading to consider their safety as controversial, especially for patients with a history of breast or endometrial cancers.  In our laboratory, the availability of in vitro mucosal cell cultures obtained from biopsies of the vaginal vestibule has represented a useful tool to evaluate the efficacy of new therapeutic strategies for vaginal atrophy. Recently, growth factors have been shown to interact with the estrogen pathway, so we investigated the proliferative effect of keratinocyte growth factor (KGF), a known mitogen for epithelial cells, on human vaginal mucosa cells, and its in vivo efficacy on vaginal atrophy in a murine model. We demonstrated that KGF restores vaginal trophism similarly to intravaginal estrogenic preparations, without systemic effects, thus suggesting its use as an alternative therapy for vaginal atrophy. An international patent has been registered for this product. In conclusion, the increasing involvement of the laboratory in translating scientific discoveries into patient care – often referred to as a “bench to bedside” process, should lead the Laboratory Medicine community to encourage specific protocols for the development of advanced therapies and their faster application into clinical practice.