"We expected different cells types to form, but their organisation into structures resembling human airways surprised us and is a very exciting result," lead author Dr. Jason Spence said.
In the method, protein ActivinA is added to stem cells and they are left for four days. A type of tissue called endoderm is formed. Endoderm is found in early embryos and gives rise to the lung, liver and several other internal organs.
Noggin, another protein, and a transforming growth factor is added. After four days the endoderm is induced to form 3D spherical structures called the foregut spheroids.
The next challenge is to make these structures expand and develop into lung tissue by exposing the cells to proteins involved in lung development.
Spheroids are transferred to protein mixture and incubated at room temperature for 10 minutes until the mixture solidifies. It is then treated with additional proteins every four days and transferred into a new protein mixture every 10-15 days.
The resulting lung organoids can survive in culture for over 100 days and develop into well- organised structures containing cell types found in the lung.
The lung organoids are self-organising, and do not require further manipulation to generate 3-dimensional tissues.
Previous studies have focused on forming the outer tissue of the lung (the epithelium). This new method goes one step further by also creating connective tissue (mesenchyme).
In a more recent study, distal airway tissue was formed, which gives rise to the small airways less than 2mm in diameter, researchers said.
With the new method, cells of the large proximal airways also form, enabling more complete study of lung development and lung diseases, researchers said.
The study is published in the journal eLife.


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