Growing 3D miniature lungs from stem cells

Chuck Bednar for redOrbit.com @BednarChuck

Researchers from the University of Michigan have cooked-up the perfect recipe for growing miniature, three-dimensional human lungs from stem cells, but you wont find this recipe in a cookbook it appears in the latest edition of the journal eLife.

Lead author Dr. Jason Spence, a professor at the UM Medical School in Ann Arbor, and colleagues from the Cincinnati Childrens Hospital Medical Center, the University of California, San Francisco (UCSF), Seattle Childrens Hospital and the University of Washington reported in their paper how they converted human pluripotent stem cells (hPSCs) into mini lungs.

Their work compliments with other recent research in the field (including building lung tissue from the scaffold of donated organs), the publishers of eLife said, and their method produces an organ that is more similar to the human lung than previous efforts because it can grow structures that closely resemble both the large proximal airways and the small distal airways.

The process

They took hPSCs (both embryonic and induced) and added a protein known as ActivinA, which is involved in lung development. They left the stem cells for four days, and during this period, a type of tissue known as endoderm formed. Found in early embryos, forms several internal organ types, including the lung and the liver.

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Next, they added a second protein a growth factor called Noggin and again left the growing tissues for four days. The endoderm was then induced to form 3D spherical structures known as the foregut spheroids. At this point, the scientists worked to make these structures expand and form into lung tissue by exposing the cells to proteins involved in lung development.

Once the spheroids were transferred into the protein mixture, they were allowed to incubate at room temperature for 10 minutes until the mixture solidified. They were treated with additional proteins every four days and transferred into a new protein mixture every 10 to 15 days.

The process is used to create lung organoids that should survive in culture for over 100 days and develop into well-organized structures containing cell types found in the lung, the study authors explained. The mini-lungs are essentially self-organizing, and once they are formed, they require no additional manipulation to generate three-dimensional tissues, they added.

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Growing 3D miniature lungs from stem cells