Disease Team Therapy Development III
Stem Cell Use:
Adult Stem Cell
There are no satisfactory conventional solutions for thousands of Californians with acquired severe airway stenosis, which is a narrowing of the airway. Airway stenosis has profound impact on quality of life, limiting the ability to breathe and communicate. Reconstructive surgery using currently available tissue flaps or grafts has failed to deliver satisfactory results, and for many, the only option is to use medical devices like tracheotomy tubes or stents, both of which can lead to infection and pain, and possible complications of erosion, blockage, bleeding, and death. Thus, overall quality of life of afflicted individuals is limited and the cost to the healthcare system, the patient, and their caregivers is disproportionately high. A solution that permits effective breathing and speaking while avoiding prosthetic airway support is highly desirable. Our team has performed a series of compassionate use tissue-engineered, stem cell based tracheal implants in adults and children with life-threatening airway stenosis. Three lives were saved and one received effective treatment of symptoms. Although ground-breaking, these procedures have left many questions unanswered, thus further investigation is required before definitive conclusions can be drawn regarding the safety and efficacy of this approach. Although compassionate use surgeries have met with initial clinical success and have garnered notable attention, there remain significant scientific gaps that must be addressed in clinically relevant preclinical studies before this technology is ready for widespread use. This project and the associated uniquely qualified team are ready to rigorously address these unanswered questions and move this new therapy to more widespread human clinical application.
Statement of Benefit to California:
The citizens of California have generously invested in stem cell research and a return on their investment will include breakthroughs in medical treatments for diseases where there are currently limited options. Tissue-engineered stem/progenitor cell-derived airway transplantation is a leading example of translational research in regenerative medicine that can be used for a host of diseases. Through this team effort scientists and physicians will lead the early promise of airway transplantation to clinical trials in California and beyond. This research team proposes to use tissue-engineered airway scaffolds with stem and progenitor cells to cure an extraordinarily difficult to manage and life-threatening health problem. Severe airway obstruction occurs in approximately 200 adults in California each year. The morbidity associated with this disease is very high, and it can be fatal for some. The knowledge gained from the tissue engineering and preclinical studies proposed will provide a new technology that can be applied to these and other disorders in California. We foresee that our stem cell-derived airway transplant could also be extended to treat an important subpopulation of children with severe subglottic and tracheal stenosis, malacia, or agenesis that have proven refractory to standard surgical interventions, and adult patients with debilitating laryngeal scarring. A further exciting possibility is that stem cell-derived airway transplants or bioengineered stents could also be applied to treat an important subpopulation of adults with severe chronic obstructive pulmonary disease (COPD). Given that the prevalence rate of COPD for California citizens greater than 65 years of age approaches 10%, if even 0.1% of COPD patients in California were candidates, specifically those with associated tracheobronchomalacia, then greater than 3,000 patients might benefit from this treatment. The methods and technology developed from this project can also be used as the basis for other similar health needs including esophageal, bladder, and bowel replacements for disorders where present treatments are very limited and impair quality of life.