Three-dimensional “mini-lungs” coaxed from stem cells and grown in a dish may offer insight into lung disease and could lead to the development of new drugs, scientists say.
Previous research has focused on deriving lung tissue from flat cell systems or growing cells onto scaffolds made from donated organs.
Researchers define the system for generating the self-organizing 3D structures that mimic the make-up and complexity of human lungs in a new study published online in eLife.
Ideas into innovations
“These mini-lungs can mimic the responses of real tissues and will be a good model to study how organs form, change with disease, and how they might respond to new drugs,” says senior study author Jason R. Spence, assistant professor of internal medicine and cell and developmental biology at the University of Michigan Medical School.
The scientists succeeded in growing structures resembling both the large airways known as bronchi and small lung sacs called alveoli.
Since the mini-lung structures were developed in a dish, they lack several components of the human lung, including blood vessels, which are a critical component of gas exchange during breathing.
Still, the organoids may serve as a discovery tool for researchers as they churn basic science ideas into clinical innovations. A practical solution lies in using the 3D structures as a next step from, or complement to, animal research.
Stomach, brain, liver, and intestine
Cell behavior has traditionally been studied in the lab in 2D situations where cells are grown in thin layers on cell-culture dishes. But most cells in the body exist in a three-dimensional environment as part of complex tissues and organs.
Researchers have already successfully generated organoids that serve as models of the stomach, brain, liver and human intestine.
The advantage of growing 3D structures of lung tissue, Spence says, is that their organization bears greater similarity to the human lung.
To make the lung organoids, researchers manipulated several of the signaling pathways that control the formation of organs. First, stem cells—the body’s master cells—were instructed to form a type of tissue called endoderm, which is found in early embryos and gives rise to the lung, liver, and several other internal organs.
100 days in a dish
Scientists activated two important development pathways that are known to make endoderm form three-dimensional tissue. By inhibiting two other key development pathways at the same time, the endoderm became tissue that resembles the early lung found in embryos.
In the lab, this early lung-like tissue spontaneously formed three-dimensional spherical structures as it developed. The next challenge was to make these structures expand and develop into lung tissue. To do this, the team exposed the cells to additional proteins that are involved in lung development.
The resulting lung organoids survived in the lab for over 100 days.
“We expected different cells types to form, but their organization into structures resembling human airways was a very exciting result,” says lead study author Briana Dye, a graduate student in the cell and developmental biology department.
Researchers from University of Washington; University of California, San Francisco; Cincinnati Children’s Hospital Medical Center; and Seattle Children contributed to the study. The National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the March of Dimes, and the University of Michigan’s Center for Organogenesis and Biological Sciences Scholars Program funded the work.
Source: University of Michigan