Lung and Tracheal Tissue Expected to Aid Respiratory Disease Research

By modifying a technique for growing cultured intestinal tissue, researchers have developed a tissue-engineered model of the lung and trachea, which contains the diverse cell types present in the human respiratory tract.

Since the cellular and molecular mechanisms that underpin regeneration of the human lung are unknown, study of lung repair has been slowed by the necessity of using model systems that exclude key components.

Investigators at Children's Hospital Los Angeles (CA, USA) had previously developed tissue-engineered small intestine (TESI) and showed that this regenerated tissue was functional and contained all of the key components of the native tissue. Based on this expertise, they hypothesized that multicellular epithelial and mesenchymal cell clusters or lung organoid units (LuOU) could be transplanted to recapitulate proximal and distal cellular structures of the native lung and airways.

The investigators described in the October 31, 2016, online edition of the journal Tissue Engineering Part C: Methods how they transplanted postnatal tissues from whole mouse and human lung, distal mouse lung, as well as mouse and human trachea onto biodegradable polymer scaffolds. The tissue obtained by using this strategy was termed tissue-engineered lung or TELu, and it contained the necessary cell types consistent with native adult lung tissue and demonstrated proliferative cells at two and four weeks. This technique recapitulated important elements of both mouse and human lungs featuring key components of both the proximal and distal lung regions.

"We think that understanding lung regeneration in this model will allow several steps forward," said senior author Dr. Tracy Grikscheit, associate professor of surgery at Children's Hospital Los Angeles. "For example, advanced stages of disease can be studied with TELu that would be impossible to fully understand in our patients. Likewise, we can more quickly apply many more therapies in this model in order to – hopefully – deliver future human therapies."

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Children's Hospital Los Angeles