CHOP Scientists Engineer Personalized Cartilage Graft for Infants with Life-Threatening Airway Narrowing
Method could be used to treat young children with severe disorders that narrow the airway and require complex surgery
Severe subglottic stenosis is a narrowing of the airway below the vocal cords and above the trachea. An estimated 20,000 infants per year are affected by this condition. The most severe cases require laryngotracheal reconstruction (LTR), an open airway surgery that is used to enlarge the airway by implanting cartilage taken from a rib cage. While LTR is used to successfully treat thousands of children with subglottic stenosis, in many cases, young children often lack enough costal cartilage – the cartilage connecting our ribs to the sternum – for these grafts. As a result, operations often need to be delayed, leaving the child attached to a tracheostomy tube until they are older, and there is a higher risk of needing follow-up surgery because the airway is at risk of narrowing again.
To improve this process and reduce the risk of these potential complications, a team led by
"We needed something that could be equivalent to a piece of cartilage, integrate well with the surrounding tissue, be well tolerated by the patient, behave like native tissues and regrow and be part of the airway," Gottardi said. "This required quite a bit of creative thinking because of the additional challenges in children who are so small and still growing."
To overcome these limitations, the researchers, led by former Gottardi lab member
Using ear-derived cartilage progenitor cells (eCPCs), which can mature into cartilage-producing chondrocytes, the researchers demonstrated that MEND can be "recellularized" after the removal of elastin and blood vessels and suitable for implantation in less than a month. This technique was validated in a preclinical in vivo model and demonstrated better performance than costal cartilage, the standard of care, with no instances of adverse events reported.
Importantly, this method needed to work in a clinically relevant timeframe. In a real-world scenario, clinicians may only have one or two months to be able to perform the procedure when it can still benefit the patient. Harvesting seed cells within days and creating a scaffold within three to four weeks is significantly less time than the six months that was typically needed for engineered cartilage. These findings will be further validated prior to proposing the procedure for patients suffering from severe subglottic stenosis.
"This research shows really promising data that suggests this novel approach could overcome the autograft-associated limitations we sometimes encounter when attempting laryngotracheal reconstruction in infants," Jacobs said. "With more research, we expect this could decrease the need for invasive surgery, and we may be able to apply the technology to other conditions that require a cartilage graft."
This study was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health grant R21HL159521, Children's Hospital of Philadelphia Research Institute, the Frontier Program in Airway Disorders of Children's Hospital of Philadelphia, the National Science Foundation Graduate Research Fellowship No. DGE 1845298, the University of Pennsylvania University Scholars Program, and American Society of Pediatric Otolaryngology research grant, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health grant P3AR0069619.
Gehret et al, "A Translational Approach to Airway Reconstruction Leveraging Decellularized Meniscus and Cartilage Progenitor Cells."
About Children's Hospital of Philadelphia:
A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania, New Jersey, and Delaware. CHOP also operates the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia, the Behavioral Health and Crisis Center (including a 24/7 Crisis Response Center) and the Center for Advanced Behavioral Healthcare, a mental health outpatient facility. Its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit https://www.chop.edu.
Contact: Ben Leach
Children's Hospital of Philadelphia
(609) 634-7906
[email protected]
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SOURCE Children's Hospital of Philadelphia
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