Researchers at the Centre of Regenerative Medicine (CReM), a joint venture between Boston University and Boston Medical Centre, have developed a method to regenerate damaged lung cells using engineered stem cells in the hope of developing a treatment that can replace lung transplants.
The team did so by using pluripotent stem cells (PSCs or stem cells that are able to develop into different kinds of cells) to create basal cells that are responsible for maintaining the airways in the lungs. They then developed methods to transplant these basal cells into the lungs of mice to see if they could regenerate damaged tissue.
“The mice and human pluripotent stem cells were differentiated into airway basal cells in the laboratory. We were then able to use these cells to reconstitute the stem cell compartment of the injured airways in mice,” Dr Darrell Kotton, a professor of medicine at the Boston University Chobanian & Avedisian School of Medicine and director of the CReM, said in a statement.
The researchers said that the technique resulted in the life-long engraftment of the engineered basal cells in the lungs of the mice they tested it on. Moreover, the procedure did not require the use of immunosuppressants (a class of drugs that reduce the immune response of the body) that is required to be taken by individuals receiving lung transplants.
“Because the cells engrafted as basal cells, the normal stem cell of the airways, they were able to self-renew or make copies of themselves by dividing and also giving rise to other cell types that together make a functional airway epithelium,” Dr Kotton added.
Replacing lung transplants
The research could lead to the development of therapeutics to treat acute injuries to the lungs resulting from conditions such as COVID-19, pulmonary fibrosis, and emphysema, in which there is progressive destruction of the epithelium (cells lining the airways) that causes reduction in respiratory function.
Currently the only method to tackle such conditions is a lung transplant, which is severely limited by a lack of supply of donor lung tissue and the risk of rejection of the transplanted organ. Individuals receiving such a drastic surgery are usually kept on immunosuppressants for life, which can make them susceptible to other infections.
“iPSCs can be made from any person with lung disease. They can be differentiated into lung stem cells in the laboratory. They can be transplanted to reconstitute the healthy airway epithelial cells in a way that is durable and functional,” Liang Ma, first author of the paper said.
Moreover, for people suffering from genetic lung diseases like cystic fibrosis and primary ciliary dyskinesia, the new technique (if it makes it into the clinical realm) will make it possible to gene-edit their iPSCs in the laboratory and then transplant them into their lungs. The newly engrafted cells will have had their gene mutation corrected, so they should be free of anomalies and function normally.
“Since these cells will be the person’s own cells, differing only in the corrected gene, in theory they should not be rejected after transplantation back into that person. This avoids any need for immunosuppression, demonstrated in our present proof-of-concept transplantation studies,” said Michael Herriges, a postdoctoral fellow in the Kotton lab.
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