Therapeutic Regeneration of Skeletal and Smooth Muscles in Female Pelvic Floor Disorders with Human Muscle-Derived Stem Cells in Animal Models.
Pelvic floor disorders, such as stress urinary incontinence, fecal incontinence and vaginal prolapse, are the major public health concerns in women. These conditions are quite common, greatly affect the quality of life, and represent significant health care costs. The prevalence of these disorders in women ranges from 15% in younger ages to 78% in nursing home residents. The yearly direct costs of urinary incontinence in the US alone were 19.5 billion dollars in 2000, an amount higher than the costs generated by HIV or breast cancer in 2005. The treatment of pelvic floor disorders in women still poses a significant challenge in current medical practice because of poor long-term success rates. Although the etiologies of these conditions in women vary, dysfunctions of the pelvic floor and vaginal support caused by damaged skeletal and smooth muscles are involved. This proposed project focuses on the use of human adult stem cells, namely muscle derived stem cells, to regenerate the defective skeletal and smooth muscles in the pelvic floor and vaginal tissues. Another goal of this study is to regenerate and repair the damaged sphincters that control urine and feces. The data obtained with this translational study could revolutionize the clinical management of pelvic floor disorders in women. Application of human muscle-derived stem cells also has the potential to alter our understanding of these debilitating conditions.
Pelvic floor disorders, including urinary incontinence, fecal incontinence, vaginal prolapse, and pelvic organ prolapse, affect a significant number of women in California with a prevalence that ranges from 15% in younger ages to 78% in nursing home residents. Risk factors for pelvic floor disorders include age, the number of childbirth, and obesity. Child birth injury to pelvic muscles, connective tissues, and nerves appears to be the most important risk factor. Aging and hormonal changes with menopause are other important risks for pelvic floor disorders. Californians are not immune to any of these risks. This translational study focuses on the investigation of the therapeutic potential of human adult stem cells derived from skeletal muscles for the treatment of pelvic floor disorders in an animal model. The long-term objective is to devise a clinical trial using autologous stem cells derived from muscles for treatment of these debilitating conditions in humans. Autologous adult stem cells are advantageous for clinical applications because they can be easily obtained in large quantities under local anesthesia and possess the capabilities to undergo long-term proliferation, self-renewal, hypo-immunogenicity, and multipotent differentiation. Safety issues regarding the use of viral transduction vectors and non-human components, such as animal feeder cells and fetal bovine serum (FBS), are not a concern because genetic manipulation is not required and autologous human serum can be used for the culture and expansion of these stem cells. The data obtained with this study could revolutionize the clinical management of these debilitating conditions for women in California. This research project will, therefore, greatly benefit the State of California and its citizens.