A UC Davis team, co-led by Alice Tarantal, PhD, and Peter Belafsky, MD, MPH, PhD, has received a $4.4 million grant from the California Institute for Regenerative Medicine (CIRM) for their project entitled “Tissue Engineered Recellularized Laryngotracheal Implants”, which proposes to develop a stem cell-derived airway transplant to cure a difficult, life-threatening problem known as severe airway stenosis.

With the funding of this disease team grant, Dr. Tarantal, CNPRC Reproductive Sciences and Regenerative Medicine Unit Leader and Professor of Pediatrics and Cell Biology and Human Anatomy; and Dr. Belafsky, Professor of Otolaryngology, will work to develop a safe and effective tissue engineered treatment for patients suffering from narrowing of the upper windpipe (trachea) and lower voicebox (larynx).

Severe airway stenosis is a life-threatening problem, which can result from head, neck, or throat cancers, as well as from trauma or rare physical conditions. According to Dr. Belafsky, it occurs in approximately 200 Californians each year and profoundly affects a person’s quality of life because it obstructs breathing and communication. Surgery, the current standard of care, can include use of tracheotomy tubes and stents, which are highly invasive, frequently providing less than satisfactory results, and can cause infection, pain, and voice loss.

Drs. Tarantal and Belafsky will be using a natural airway scaffold developed from a decellularized tracheal template with stem/progenitor cells from the patients themselves to create the tissue engineered implant. They hope to complete the necessary steps in order to conduct a Phase I clinical trial in the near future. The CIRM disease team grant enables the UC Davis team to first focus on an initial two years of preclinical and investigational new drug (IND)-enabling studies.
“There are a number of scientific questions that we plan to explore in the next few years,” said Dr. Tarantal, who also serves as Associate Director of the UC Davis Stem Cell Program. “We will develop and refine optimal transplantation techniques as well as determine the fate of implanted stem and progenitor cells for these implants. Firmly establishing safety and efficacy is critical to the goal of a transformative treatment for human patients.”

“The knowledge gained from these preclinical studies will provide us with a window into a new technology that could potentially be applied to other disorders in other organ systems,” said Dr. Belafsky, who also serves as Medical Director of the Voice and Swallowing Center at UC Davis. “Stem cell-derived, tissue engineering techniques could be extended to also treat children who suffer from severe laryngeal conditions that surgery cannot cure.”

“Stem cell-derived airway transplants or bioengineered stents also might be used for a vast array of airway diseases,” he adds. “The methods and technology developed in this research could also be used to treat disorders that require esophageal, bladder, or bowel replacement, where the current standards of care remain very limited and impair quality of life.”

This laryngotracheal reconstructions proposed are based on findings from European compassionate use exemptions in five dying patients, saving three of their lives. First-in-human studies were performed by University of London colleague and UK partner and collaborator, Dr. Martin Birchall. These compassionate use cases highlighted important gaps in knowledge and the critical need for preclinical studies in nonhuman primates to address questions of safety and long-term efficacy. Stem/progenitor cell-derived airway transplants that use the patients’ own cells have the clinical advantage of not requiring anti-rejection medications.

To read the UC Davis Health System press release, go to:http://www.ucdmc.ucdavis.edu/publish/news/newsroom/8535