Cellular Blueprint for Lungs Could Help to Develop Regenerative Lungs
Yale researchers created a human lung cellular blueprint through refined screening across animal species that will help to understand the design principles behind lung function and diseases and to bioengineer new lungs.
The two Yale laboratories under Naftali Kaminski, M.D. and Laura Niklason, M.D., Ph.D., published their study in Science Advances on December 4.
The researchers used single-cell technology to analyze the critical cell interactions and found similar interactions in four animal species; rat, pig, mouse, and human. The study revealed cell interactions behind various cellular functions like cell signaling, cell regulation, and disease monitoring and provided vital information about mechanisms behind lung development and lung diseases.
Micha Sam Brickman Raredon, the first author of the study and the M.D./Ph.D. candidate in Niklason’s lab, said the researchers were able to measure all the cell types from any organ or tissue from a single snapshot.
Five years ago, “we didn’t have the resolution to look at individual cells and how they behave,” said Kaminski, the Boehringer-Ingelheim Professor of Internal Medicine and professor of pharmacology. “It’s like we have moved the resolution on cell analysis from looking at the night sky withthe naked eye to a child’s telescope to an observatory and, now, the Hubble telescope.”
There are nearly 40 different types of cells in the lung and hundreds of thousands of cells, each with tens of thousands of genes. It’s challenging to generate a blueprint of cellular interactions that show which cell mechanisms are related to normal functioning as the cell contents can change quickly in response to different conditions.
But the Yale researchers were able to create a blueprint through the network approach.
Nikalson was working on a project to develop regenerative lung tissue. For that, they required insights about how cells interact in lung tissue.
Raredon referred to the process of regenerating lungs from one’s own body issue to “the Holy Grail.” Last stage lung diseases have high mortality and morbidity. The only possible way to fight the disease is a lung transplant, which is often rejected by the body’s immune system. Extensive drugs are used to suppress the immune system, but they have their own side effects.
Nikalson and his team are developing various stages of regeneration inside custom-designed glass jars. They had been growing lung tissues in glass jars providing necessary chemical and mechanical stimuli to grow them to organs.
They could now compare their engineered lung constructs to this blueprint, which shows specific signals present in all species that they want to reconstitute. The cellular blueprint for lungs will also help to find the potential therapeutic targets for diseases like idiopathic pulmonary fibrosis.
Now the scientists will be able to bioengineer new organs with the help of information on how cells communicate in the lungs and how it is conserved across species.
Kaminski and his team were looking at the basic principles behind the development of an organ, and the findings could assist in the bioengineering of new organs.
Author : Namitha Thampi