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Research in Mice May Lead to Human Model of Tracheal Replacement

Radiographic and Histological Characteristics of Decellularized Trachea in a Mouse Model of Tracheal Replacement

On-Demand Content—Best of Scientific Oral Presentation

Lumei Liu, PhD

 

There is no current standard of care for tracheal replacement—but researchers are working on it.

“Attempts to replace the trachea remain heroic and have had highly variable results,” said Lumei Liu, PhD, of Nationwide Children’s Hospital in Columbus, Ohio. “There are no approaches that can replace the native trachea with tissue identical to the host.”

Decellularized trachea, however, provides a promising solution. Dr. Liu and Sayali Dharmadhikari, MS, also of Nationwide Children’s Hospital, explored radiographic changes of decellularized tracheal grafts in a mouse model of orthotopic implantation.

“Some of the earliest clinical applications of tissue engineering have been based from decellularization due to its affinity for regeneration,” said Dr. Liu. “Decellularized trachea provide a 3D scaffold that possess the biophysical and biochemical cues necessary to support host-derived regeneration while removing all donor cellular material. Specifically an ideally decellularized trachea would create a scaffold that preserves the native extracellular matrix while removing all immunogenic material. Our work is devoted to the rational design of tissue engineered trachea for long-segment tracheal defects. We have defined the critical barriers to graft translation in tracheal replacement and are identifying how we can modulate decellularized tracheal scaffolds to accelerate graft regeneration.”

The process, however, is not quite ready to be practiced on human patients.

“Our work represents a proof of concept that implantation of decellularized trachea are able to regenerate an epithelium that is identical to native epithelium,” said Dr. Liu. “However, the mechanisms driving graft regeneration must be defined in order to translate our technology to the bedside. We are using a combination of in vitro, in vivo, and computational models that will not only permit the definition of these mechanisms but allow us to qualify the effect of graft modifications.”

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