A cell based preventive strategy for birth induced pelvic floor disorders.

Pelvic floor disorders (PFD) affect nearly one third of pre-menopausal and nearly half of postmenopausal women. PFD include pelvic organ prolapse, urinary and fecal incontinence and may be perceived as severe as stroke or dementia. The most important risk factor is vaginal birth. It causes direct trauma to the pelvic floor nerves and its supportive connective tissues and muscles. In most women, damage remains initially hidden, but surfaces later in life. The current treatment is surgery, with reasonable success for urinary incontinence, high recurrence rates for prolapse and deceiving results for anal incontinence. Prevention by prelabor cesarean section sounds tempting but is unrealistic. We propose prevention by action immediately after delivery by stimulation of the spontaneous repair mechanisms using stem cells, earlier harvested from the patient. We propose a stem cell called mesangioblast (MAB) because it can regenerate muscle and may also contribute to nerve recovery. MABs may work through local temporary release of factors promoting healing, but when they are from the same individual they may engraft and help repair injured structures and their function. Using MAB is realistic: they can be derived from simple needle muscle biopsies, expanded in the lab and reinjected into the host. This is already done in trials for muscle dystrophy patients. The current project will produce evidence of this concept by testing in a rat model for vaginal birth trauma.