‘Lung-on-a-Leaf’ May Aid Studies into Pulmonary Diseases, From Fibrosis to Inflammation

The Arizona Biomedical Research Commission awarded a $750,000 grant to researchers at University of Arizona (UA) College of Medicine for their innovative, plant-based model system — a “lung” growing on a leaf — to study pulmonary diseases that range from fibrosis to inflammation and infection.

The three-year grant was given to Kenneth Knox, MD, a professor of medicine and immunobiology and associate dean, and Frederic Zenhausern, PhD, director of the UA Center for Applied NanoBioscience and Medicine.

“The lung is a very complex organ,” Knox said in a press release. “There are not many novel ways to study the lung, but growing cells on a leaf would be a way for us to organize cell types in a biologically meaningful way to learn more about lung immunity and lung fibrosis.”

The idea to grow lung cells on a leaf came after Knox became aware of the work of other UA researchers, who were developing a tumor model system using spinach leaves. This system aims to more accurately reproduce interactions of cancer cells and to assess outcomes of various cancer therapies.

As a pulmonologist, Knox realized that the branching structure of a plant leaf is very similar to that of the lung, and wondered if this technology might be used to create a “lung on a leaf” model.

Previous work in Zenhausern’s lab led to the development of an in vitro grown gut on a chip, which is now being used to understand the complex interactions between cells and the microbiome, the natural collection of microbes that populate the human gut.

This approach will allow researchers to understand how cells respond to certain drugs, knowledge that will allow the development of personalized therapies.

“We are developing a tool that will better mimic the human system and improve the overall concept of personalized medicine,” Zenhausern said. “We now can think about the long vision because we have those building blocks. If we can put a lung on a leaf, maybe next it will be a liver, or another organ.”

For the lung model, researchers first treated the leaf with detergents to remove all plant cells, as well as DNA and proteins, leaving only the branches (the structure). This then is used as a scaffold to repopulate the branches with different cell types, creating a model to mimic the lungs’ architecture.

By the the third year of their grant, researchers hope to use human patient cells and build a patient-personalized 3D model.

This model might not only allow researchers to study the mechanisms underlying lung fibrosis but also lung infection, and inflammatory conditions like sarcoidosis, a multi-system inflammatory disease that predominantly affects the lungs and intrathoracic lymph nodes.

If successful, this approach might mean that research into human diseases and therapies can take place in lab dishes, avoiding the need for animal studies.

“We are at a point in medicine where collaborations across disciplines are needed to take us to the next level,” Knox said. “Our goal is to move the field forward in how we model different lung diseases.”