Researchers in the University of Michigan have cooked-up the perfect recipe for growing miniature, three-dimensional human lungs from stem cells, however, you won’t find this recipe inside a cookbook C it appears in the latest edition of the journal eLife.
Lead author Dr. Jason Spence, a professor in the UM School of medicine in Ann Arbor, and colleagues in the Cincinnati Children’s Hospital Clinic, the University of California, Bay area (UCSF), Seattle Children’s Hospital and the University of Washington reported within their paper how they converted human pluripotent stem cells (hPSCs) into mini lungs.
Their work compliments along 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 a body organ that’s more similar to the human lung than previous efforts because it can grow structures that closely resemble both the large proximal airways and also the small distal airways.
They took hPSCs (both embryonic and induced) and added a protein known as ActivinA, that is involved in lung development. They left the stem cells for four days, and through this period, a kind of tissue known as endoderm formed. Present in early embryos, forms several internal organ types, such as the lung and the liver.
Next, they added another protein C a growth factor called Noggin C and again left the growing tissues for four days. The endoderm was then induced to form 3D spherical structures referred to as 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 with lung development.
Once the spheroids were transferred in to the protein mixture, these were permitted to incubate at 70 degrees for 10 minutes until the mixture solidified. These were given additional proteins every four days and transferred right into a new protein mixture every 10 to 15 days.
The process is used to produce lung organoids that should survive in culture for more than 100 days and become well-organized structures containing cell types based in the lung, the research authors explained. The mini-lungs are essentially self-organizing, and once they’re formed, they require no additional manipulation to generate three-dimensional tissues, they added.
Unlike previous methods, which centered on forming the outer tissue of the lung (the epithelium), this new technique allows scientists to create connective tissues (mesenchyme). Additionally, their method allows cells of the large proximal airways to create along with the ones from the small airways, that allows for a more complete study from the growth and development of lung tissues and diseases.
Alternatively, the researchers said that their method could be altered to have the foregut spheroids put into a lung scaffold from the human lung declared unsuitable for transplantation to make the organoids mature more quickly. Furthermore, stem cell lines from patients with genetic disorders that impact lung development can be produced (or mutations induced) in order to study how mutations affect cell differentiation, tissue organization, and tissue growth.
Since the structured were developed in a laboratory dish, however, they lack several key areas of an actual lung, including arteries. Dr. Spence and his colleagues hope to build upon their findings and create more complicated mini-lungs with the addition of these missing components, with the objective of ultimately creating organoids that capable of performing functions related to respiration.
