Led by a renowned throat surgeon and a highly regarded stem cell researcher, a UC Davis team has received a $4.4 million grant from the California Institute for Regenerative Medicine (CIRM) to develop a stem cell-derived airway transplant to cure a difficult, life-threatening problem known as severe airway stenosis. The funding was part of the agency’s Disease Team grants.
With the grant, Peter Belafsky, professor of otolaryngology and principal investigator for the new study, and Alice Tarantal, professor of pediatrics and cell biology and human anatomy, and the project’s co-principal investigator, will work to develop a safe and effective tissue-engineered treatment for patients suffering from the critical 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 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.
Belafsky and Tarantal propose using a tissue-engineered airway scaffold with stem/progenitor cells from the patients themselves – sort of a biological infrastructure for the cells to develop and grow – to create a viable implant. They said that within four years it could be possible to complete the necessary steps for a successful stem-cell derived airway transplant in a later-stage clinical trial, and perhaps develop it for commercialization. The CIRM 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 Tarantal, who is also Reproductive Sciences and Regenerative Medicine Unit leader at the UC Davis California National Primate Research Center and serves as associate director of the university’s Stem Cell Program. “We will develop and refine optimal transplantation techniques as well as determine the fate of implanted stem and progenitor cells for tissue-engineered airway implants. Firmly establishing the safety and efficacy of this process is critical to the goal of a transformative treatment for human patients.”
Belafsky noted that the UC Davis team is uniquely positioned to address many of the clinical and scientific questions involved in regenerative medicine and tissue engineering. It already has experience in successfully using stem cell-based tissue engineered tracheal implants. And in 2010, a team co-led by Belafsky successfully performed the world’s second documented larynx transplant. The team’s new research effort could yield results that have benefits well beyond addressing patients with a life-threatening narrowing of airway.
“The knowledge gained from our preclinical studies could easily provide us with a window into a new technology that can be applied not only to airway stenosis, but to disorders affecting other patient groups and other hollow organs as well,” said Belafsky, who also serves as medical director of the Voice and Swallowing Center at UC Davis. “Stem cell-derived tissue engineered techniques could be extended to 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 disease,” added Belafsky. “The methods and technology developed with our project could also be used to treat health disorders that require esophageal, bladder or bowel replacement, where the current standards of care remain very limited and impair quality of life.”
Belafsky and Tarantal said their laryngotracheal reconstruction work is based on some initial preclinical studies that documented rapid cartilage regeneration and epithelial (tissue) re-growth, which suggests that their technique has the potential to restore normal breathing and communication abilities in study subjects. The CIRM-funded research includes an important collaboration with a team in England led by Martin Birchall, associate professor in otolaryngology at UC Davis and professor of laryngology at England's University College London.