Grant Award Details
- The objective of this project is to identify a development candidate for the treatment of female urinary incontinence using iPSC-derived smooth muscle precursor cells (SMPC) and smooth muscle cells (SMC).
Grant Application Details
- Autologous iPSC Therapy for Urinary Incontinence
Urinary incontinence (UI) is common and serious, with two-thirds of the burden borne by women. UI impacts both quality and length of life; women with UI suffer debilitating falls, experience social isolation and are clinically-depressed more commonly than continent women. UI is the primary reason for elderly women to be institutionalized and carries an annual healthcare cost that exceeds $20 billion in the USA. Up to 7 million Californian women are affected with UI, a number forecast to increase by 55% in 2010 to 2050. Surgery is the main treatment today but results can be variable with a need for repeat surgeries in 30-50% of women. Here, we describe our intended target product for UI based on FDA-compatible stem cells and a minimally-invasive route of delivery that is very familiar to physicians and is currently used for injection of bulking materials to treat UI. Our stem cell approach has the potential to provide an unlimited source of cells for tissue engineering and regenerative medicine. Thus, as an added benefit associated with this research, we establish a foundation for broad applications in women’s health including disorders that affect the same type of cells as in UI, smooth muscle, such as diseases of the blood vessels, respiratory tract (e.g., chronic obstructive pulmonary disease-COPD and asthma), digestive system (e.g. gastroesopageal reflux disorder-GERD and motility disorders) and others secondary to diabetes, neurodegeneration and common health problems.
Consider the tragic statistics that today the annual sale of diapers for urinary incontinence (UI) in women exceeds that of diapers for babies and that UI is the most common reason for families to institutionalize their elderly female relatives. The life expectancy of California women now exceeds 82 years. As we age, common age-associated tissue degeneration is a major physical, social, cultural and financial burden. Thus, UI is a major quality of life issue and public health concern both in terms of care and budgets. Overall, UI affects a staggering number of women resulting in annual health costs that exceed $20 billion nationally, a cost comparable to that of arthritis and greater than that of breast cancer and all gynecological cancers combined. Currently surgery is the most common treatment for UI, with good short-term but poor long-term data. Repeat surgeries are more morbid and have decreased efficacy; current alternatives provide even less relief. We suggest that we can “do better” by the women of California through step-wise research that leverages: 1) Small clinical trials that have already been conducted, 2) ability to produce large numbers of relevant cell types for UI treatment, and 3) unique expertise of our team. Our research overcomes major limitations to provide a ready stem cell-derived target product that we anticipate will provide a safe and effective treatment of UI resulting in improved quality of life of a significant fraction of our population.
- Stem Cells Dev (2016) Smooth Muscle Precursor Cells Derived from Human Pluripotent Stem Cells for Treatment of Stress Urinary Incontinence. (PubMed: 26785911)
- Macromol Biosci (2015) Long-Term Controlled Protein Release from Poly(Ethylene Glycol) Hydrogels by Modulating Mesh Size and Degradation. (PubMed: 26259711)
- Biomater Sci (2015) Effects of the poly(ethylene glycol) hydrogel crosslinking mechanism on protein release. (PubMed: 26539660)
- Regen Med (2015) Bilayered vascular graft derived from human induced pluripotent stem cells with biomimetic structure and function. (PubMed: 26440211)
- Sci Rep (2015) Dynamic and social behaviors of human pluripotent stem cells. (PubMed: 26381699)
- PLoS One (2014) Rapid and Efficient Conversion of Integration-Free Human Induced Pluripotent Stem Cells to GMP-Grade Culture Conditions. (PubMed: 24718618)
- Stem Cells Dev (2014) A Modified Method for Implantation of Pluripotent Stem Cells under the Rodent Kidney Capsule. (PubMed: 24800694)
- Biomaterials (2014) Engineering interpenetrating network hydrogels as biomimetic cell niche with independently tunable biochemical and mechanical properties. (PubMed: 24331710)
- Eur J Obstet Gynecol Reprod Biol (2014) Proliferative behavior of vaginal fibroblasts from women with pelvic organ prolapse. (PubMed: 25461341)
- J Minim Invasive Gynecol (2014) Histologic characteristics of vaginal cuff tissue from patients with vaginal cuff dehiscence. (PubMed: 24316139)
- Stem Cells Transl Med (2013) Reprogramming of Fibroblasts From Older Women With Pelvic Floor Disorders Alters Cellular Behavior Associated With Donor Age. (PubMed: 23341439)
- Stem Cell Res Ther (2013) Generation and characterization of transgene-free human induced pluripotent stem cells and conversion to putative clinical-grade status. (PubMed: 23890092)
- Stem Cells Transl Med (2013) Concurrent Generation of Functional Smooth Muscle and Endothelial Cells via a Vascular Progenitor. (PubMed: 24311701)