Urinary incontinence (UI) is a major health issue that affects more than 200 million people worldwide. Stress urinary incontinence (SUI), which accounts for half of all UI cases, is the involuntary loss of urine in the absence of a detrusor contraction. SUI occurs as a result of weakened muscles of the pelvic floor and urethra, producing urine loss whenever there is an increase of intra-abdominal pressure, such as coughing, sneezing, and laughing. Currently there is no effective treatment for SUI. Because weakened muscles and nerves in the urethra are the underlying cause of SUI, this proposed study seeks to correct such deficiencies by replenishing the affected urethra with human embryonic stem cells (hESC).
Human ESC are capable of differentiating into various cell types including smooth muscle, striated muscle, and nerves. These cell types are also found in the urethra and are affected during the disease progression of SUI. In Specific Aim 1 of this proposed project we will investigate whether hESC can be induced to turn into cell types found in the healthy urethra.
In Specific Aim 2 we will test the therapeutic efficacy of hESC. Because it is unethical to conduct this research in patients, we will employ a rat SUI model that was developed in our laboratory 11 years ago. We have shown in several publications that this SUI model closely mimics human SUI in both the disease progression and pathology. We are therefore confident that this rat model will allow us to assess the therapeutic effectiveness of hESC. This assessment will then help us to decide whether hESC is suitable for human therapy.
Statement of Benefit to California:
Urinary incontinence (UI) is a major health problem worldwide; therefore, this proposed study will not just benefit California but the whole world. If there is anything specifically Californian, that would be the research team and the use of human embryonic stem cells (hESC) that are federally restricted. In other words, the research has the potential to strengthen California's leadership in both the UI and hESC research fields. In the long term this enhanced leadership may translate into economic gains for California such as investment in the biotech industry and health care system. If permitted by regulatory agencies at the federal and state levels, clinical trials for this stem cell therapy could perhaps be initiated in California and therefore benefit Californians firsthand.