Non-cellular regenerative medicine techniques for prevention of female pelvic floor disorders
Professor Margot Damaser, Cleveland Clinic Foundation
One of the greatest risk factors for development of pelvic floor disorders is vaginal delivery of children, which can damage the nerves and muscles responsible for continence in addition to the connective tissues responsible for the position of pelvic organs. Without complete nerve regeneration, the muscles can atrophy. Pelvic floor connective tissue can fail to restore the vascularisation necessary for full regeneration. Current treatments, such as an implanted mesh or sling, can have a high rate of complications and a high revision rate. Regenerative interventions done soon after delivery of children, prior to muscle atrophy, has the potential to have an increased success rate and to prevent pelvic floor disorders.
Regenerative medicine usually involves local treatment with autologous stem or progenitor cells. This approach has had mixed results in clinical trials with women with stress incontinence. The mechanism of action of these cells is likely via their secretions. Therefore, a non-cellular approach with fewer risks could be to give the secretions of stem cells rather than inject the cells themselves. This approach also holds the promise of providing an off-the-shelf treatment.
This talk will summarise our preclinical studies which demonstrate that treatment with secretions of cells provide a strong regenerative effect, even when given systemically. In addition, Professor Damaser will present preclinical data demonstrating that electrical stimulation could also promote neuro-regeneration and facilitate repair. Non-cellular therapies, such as these, given soon after childbirth in women at greatest risk of development of pelvic floor disorders hold great potential to improve the lives of many women.
Preclinical animal models for pelvic organ prolapse
Professor Jan Deprest, UZ Leuven
The cause of pelvic organ prolapse (POP) is multifactorial yet includes a complex interplay between genetic factors, vaginal birth-induced trauma, aging and lifestyle. Currently, surgery is the mainstay of therapy and the life-time risk is 19% by the age of 802. Given the relevance of the condition and the failure of current strategies a better understanding of the genesis of POP and the potential for its prevention or improving current therapies appropriate animal models are required. Finding an optimal model is challenging, since humans are bipedal, have no tail, and the foetal head is relatively large compared to the pelvic dimensions, making vaginal delivery more traumatic when compared to other species. This talk will discuss both pelvic organ prolapse and birth induced injuries in animal models
Safety and performance of a wireless implantable tibial nerve stimulator device, for the treatment of patients with overactive bladder (OAB)
Dr Guri Oron, BlueWind Medical
Overactive bladder (OAB) affects millions of people worldwide with neuromodulation offering treatment option for refractory patients. A novel peripheral implantable neurostimulator device for the treatment of OAB was developed (RENOVA iStim™ system), which electrically stimulates the tibial nerve at the site just proximally of the medial malleolus. The implant is wirelessly powered by a wearable unit that controls the therapeutic parameters and is worn by the patient during treatment at home. A Clinician Programmer is used to remotely set individual stimulation parameters. Herewith, the safety and performance of the RENOVA iStim™ system is being observed for the treatment of OAB. Short term; 6-mos results, and long term; 24-mos partial results, will be presented.
Mechanical and etiological aspects of female pelvic floor disorders
Dr Pedro Martins, University of Porto
It is commonly accepted that Pelvic floor disorders (PFD) have many risk factors. However, there is no consensus on their scope and importance. Some are specific for an individual (number of pregnancies) others common to a group or population. A complete and coherent map of prolapse etiology remains an open question.
The complexity of PFD led to different, often complementary, research efforts. The mechanical behaviour of pelvic tissues, is intimately linked with their ‘normal’ and ‘diseased’ status; also influenced by individual characteristics (age, hormonal status, etc.). This led to studies on the changes in the morphology and biomechanics of pelvic tissues using animal models, since it is not feasible (materially, ethically, etc.) to conduct some research on humans. These studies are designed to clarify the scope of each PFD risk factor.
A new and promising frontier lies on the fusion of statistical/epidemiologic information with individual-level knowledge. The estimation of tissue’s mechanical behaviour based on patient specific data, may in turn, feed epidemiologic models with predictive capabilities. Such models bring an array of possibilities and implications - improved clinical diagnostics, PFD risk assessment, improved surgical outcome estimation, etc. To build such tool(s) will require a multidisciplinary effort, between medical doctors, engineers, and mathematicians.
Tissue engineering and regeneration: regulatory routes to the clinic
Ms Alison Wilson, CellData Services
Developing a new medical product requires an understanding of the regulatory environment: how the law views the product and which agencies must be involved in the process. This talk will highlight the different ways in which regenerative medicine products can be regulated in the UK/EU, which in turn dictates how they can be brought into clinical use. Authorisation for clinical trials, processes and supporting data requirements are all entirely dependent upon how a TE/RM product is regulated: as a medical device, a human tissue product or a medicinal product / ATMP. Although perhaps not as exciting as the scientific and clinical challenges involved, an appreciation of the regulatory position early in the process can only increase your chances of successfully developing a safe, effective product that reaches patients in a timely way.