Dennis Wigle, M.D., Ph.D.: So it's actually a very exciting time in the space of lung regeneration right now with a number of technologies that have really leapt forward in the last couple of years and have really made it a potential clinical reality that you really might be able to take cells from a patient, use things like decellularized matrices in order to be able to repopulate a lung matrix and really build an artificial or new lung for someone. Now that's obviously all at a research stage right now, but what was really science fiction, you know, going back four, five years ago, there's now a number of individual pieces of technology that, when you bring those together, have really made the potential to be able to build new lungs artificially a potential clinical reality.
So if you look at the hundreds of thousands of patients that currently have end-stage lung disease just in the United States alone, let alone many fold greater number throughout the world, there's a large number of people that really are not candidates for lung transplantation or other potential therapies, of which a very small number might actually be candidates for, that don't really have any other treatment options. If you look at the whole population of people dying of lung cancer in the United States every year, there's almost 180- to 190,000 people every year that are gonna die of that disease. So the potential to be able to build new lung tissue, whether it's a whole lung, whether it's parts of a lung, whether it's to just make an existing lung that isn't working well work better, there's a huge unmet patient need here in terms of people that are either suffering or either dying also from these diseases where these technologies could potentially be applied.
It's a very exciting time. There's obviously a lot of work that needs to be done in order to really translate these technologies into something that's useful for patient care. But the future is very bright, and there's obvious progress here where you can envision this being a clinical reality, where going back even five years ago or more it was really just science fiction at that point.
Regenerative medicine has the potential to provide innovative new therapies for people with lung diseases, including chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, cystic fibrosis, pulmonary arterial hypertension and bronchiolitis obliterans.
Currently, end-stage lung disease is treated with a gamut of medications or ultimately, lung transplantation. However, there is an ongoing shortage of donor lung tissue amenable to transplantation.
Research into lung preservation, lung recellularization and stem cell biology in the Center for Regenerative Biotherapeutics is leading to the development of new regenerative therapies for people with a wide range of lung diseases. Stephen D. Cassivi, M.D., and Dennis Wigle, M.D., Ph.D., both at Mayo Clinic's campus in Rochester, Minnesota, lead these efforts.
Recellularization of decellularized lungs
Mayo Clinic researchers are studying lung decellularization and recellularization techniques to move toward a goal of on-demand production of patient-specific, transplant-ready lungs.
Lung decellularization involves removing all the cells from a donor lung, leaving behind just the native architecture that can be repopulated (recellularized) with induced pluripotent stem (iPS) cells acquired from the patient's own tissues.
Mayo researchers are working to generate a functioning lung that is suitable for transplantation by first recellularizing an acellular porcine lung. Given promising results in animal models, Mayo Clinic investigators are now attempting to recellularize human lungs. Ongoing work involves differentiating iPS cells into lung-specific cells for recellularization.
Stem cell engineering
To better understand how to effectively and consistently produce patient-specific iPS cells for lung-related clinical application, Mayo Clinic researchers are conducting a clinical trial in which iPS cells can be generated from small skin biopsies taken from patients with end-stage lung disease.
Investigators believe that with further research, iPS cells could be differentiated into patient-specific pulmonary epithelial cells and delivered back to patients via cell therapy. These cells could also be used to repopulate acellular lung scaffolds for implantation.