Lung stem cell telomere extension to enable regenerative medicine


Nanoparticles deliver mRNA to the lung stem cells, extending their telomeres in hours sufficiently to reverse years of telomere shortening.


The stem cells are able to divide a few more times to continue to repair and regenerate the lung.


Daughter cells of the stem cell differentiate into AT1 cells that build and repair the walls of lung alveoli.

Short telomeres and pulmonary fibrosis

Throughout life chronic insults damage the lung. The lung stem cells need to divide to repair the damage. When cells divide their telomeres shorten, and when telomeres become too short the stem cells can no longer divide to regenerate the lung. Fibroblasts fill the resulting void with fibrosis. Telomerase mRNA extends lung stem cell telomeres so they can divide to regenerate the lung. IPF patients have very short telomeres, and telomere length predicts survival of IPF patients. In the bleomycin mouse model of pulmonary, fibrosis telomere extension using telomerase mRNA almost entirely preserves healthy lung tissue, reduces fibrosis, and increases survival.