Researchers at Columbia University Irving Medical Center have successfully grown fully functional lungs in mouse embryos using transplanted stem cells.
Many types of lung diseases are progressive and ultimately prove fatal. The only hope for patients suffering from these incurable conditions is a lung transplant; however, many millions of patients die from their diseases due to the extremely limited supply of donated organs.
If researchers can grow organs in animals, this could serve as an alternative treatment. Considerable research is being conducted in this area and various techniques have been used to grow lung tissue. These include using synthetic scaffolds to support the lung tissue as it grows and even stripping the original cells from lungs and growing new lung cells from stem cells. Significant advances have been made, but no research team has succeeded in growing fully functional lungs that are capable of transplantation that will support life. To date, it has not been possible to create the complex structures necessary for efficient gas exchange.
The Columbia University researchers opted for a different tactic and used a conditional blastocyst complementation (CBC) approach, where organogenesis is initiated using donor pluripotent stem cells inside living animals. This approach is advantageous, as it allows researchers to use the animal’s natural signals to help differentiate the stem cells into lung tissue. The researchers started the process with a tissue culture that was used to proliferate donor stem cells while maintaining their pluripotency. Those donor pluripotent stem cells were then introduced into two different types of engineered mouse embryos
One of the mouse embryos had been engineered so that it could not produce its own stem cells that were capable of developing into mature lung cells. The other could not produce sufficient numbers of lung cells to form a fully functional pair of lungs.
In both cases, the introduced stem cells outcompeted the mouse cells for the growth-promoting molecules and the mice formed fully functional lungs that allowed them to live well into adulthood. The introduced stem cells were implanted before the immune system had developed, which explains why the implanted cells were not rejected.
The researchers note that the signals required for lung development are similar across many different species, so it is conceivable that lungs could be grown in animals which could then be transplanted into humans. The researchers are now planning studies in larger animals and will conduct tests to determine whether interspecies lung transplants are possible.
The study is detailed in the paper – Generation of functional lungs via conditional blastocyst complementation using pluripotent stem cells– which was recently published in the journal Nature Medicine. DOI: 10.1038/s41591-019-0635-8