Tissue Engineered Recellularized Laryngotracheal Implants

The goal is to bring a safe and effective therapy to adult patients with critical narrowing of the upper windpipe (trachea) and lower voicebox (larynx). Our intent is to implement all of the necessary steps for a successful new stem/progenitor cell-derived airway transplant for later stage clinical trials and/or commercialization within 4 years. Our team builds on first-in-human surgical successes with stem cell-based tissue engineered airway implants in compassionate use cases in adults and children. To this end, we will perform the necessary preclinical studies to support a successful IND application within 2 years, followed by a Phase I trial in 10 patients with 1 year of follow-up. We propose to use stem/progenitor cells from the patients themselves to treat an extraordinarily difficult to manage health problem, namely large airway stenosis. This causes severe airway obstruction, which severely limits quality of life, exercise tolerance, communication, and social and employment opportunities. Occasionally, the stenosis may also be life threatening. It occurs in approximately 200 individuals in California each year. Treatment costs for these patients are very high, and the personal and societal investments are substantially higher, although outcomes are consistently poor. The endpoint desired is normal airway and lung function and an improved quality of life. Our team aims to eliminate the need for repeated surgical interventions and/or the use of stents (metal or plastic tube implants), which are not necessarily successful, yet presently the standard of care for such patients.

In 2008/2010, we used stem cell-based, engineered tracheal implants to successfully save a young woman's and a child's life. Both are very well at 5 and 3 years post-implantation. These first-in-human studies emphasize that our goal is realistic, but also highlighted the gaps in our knowledge. Specifically, there is a need for preclinical studies to address questions of safety and long-term maintenance of airway, as well as to determine the fate of the implanted cells; secondly, if supported by these preclinical safety studies, there is a need for a formal clinical trial in patients of our candidate airway implant. Stem/progenitor cell-derived airway transplants that use the patients' own cells have the clinical advantage of not requiring anti-rejection medications. Our experience, to date, indicates such medication is not needed and this finding represents a scientific and clinical breakthrough in organ transplantation. While medical benefit was demonstrated in these two preliminary patients, there is substantial work to be done before such transplants can be considered routine for patients. We address this challenge with our team approach and emphasize the synergism that occurs when linking team members from California and a partner institution, with expertise in a variety of scientific and medical disciplines to address this critical need.