Stem cell research has long been seen as a new frontier for disease therapeutics. By coaxing stem cells to form 3D miniature lung structures, University researchers are helping explain why.

In a collaborative study, University researchers devised a system to generate self-organizing human lung organoids, or artificially-grown organisms. These organoids are 3D models that can be used to better understand lung diseases.

Jason Spence, the assistant professor of internal medicine and cell and developmental biology, who was a senior author of the study, said one of the key implications of these lungs is the controlled environment they offer for future research.

“These mini lungs will allow us to study diseases in a controlled environment and to develop and test new drugs,” he said.

Specifically, Spence said, scientists will be able to take skin samples from patients with a particular form of a lung disease, reprogram the cells into stem cells and then generate lung tissue for further study. He said by analyzing the disease in a controlled environment, researchers can gain insight into the progression of various diseases and then tailor drugs for treatment.

Rackham student Briana Dye was also a lead author of the study. She said the team manipulated numerous signaling pathways involved with cell growth and organ formation to make the miniature lungs.

First, Dye said the scientists used proteins called growth factors to differentiate embryonic stem cells into endoderm, the germ layer that gives rise to the lungs.
Different growth factors were then used to cause the endoderm to become lung tissue.

“We add specific growth factors, proteins that turn on pathways in the cells, that will then cause them to lift off the monolayer so that we have this 3D spherical tissue,” she said.

Previous research has used stem cells in a similar manner to generate brain, intestine, stomach and liver tissue. Dye said one of the advantages of stem cell research is its direct path to studying human tissue.

“We have worked with many animal models in the past,” Dye said. “Animal models present obstacles because they don’t exactly behave the way human tissue and cells do. This is why stem cells are so promising.”

In the future, Spence said researchers hope to use stem cells to replace diseased lung tissue and generate new lungs. Though he said the future is promising, he stressed patience with the process.

“In terms of tissue replacement and regenerating new lungs for regenerative medicine, that’s a much more ambitious goal way down the road, we are still far away from that.”

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