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.
In their end stages, these diseases are today treated with medications or lung transplants, though there is an ongoing shortage of donor lungs that are acceptable for transplantation.
Research into lung preservation, lung recellularization and stem cell biology in the Center for Regenerative Medicine 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 of Mayo Clinic in Rochester, Minn., lead these efforts.
Ex vivo lung perfusion. Though lung transplants can be lifesaving for people with end-stage lung disease, few donors have lungs suitable for transplantation.
A recent clinical trial has shown that ex vivo lung perfusion has the ability to expand the number of potentially transplantable donor lungs. During ex vivo lung perfusion, donor lungs that are not acceptable for transplantation are treated with specific fluids for several hours to heal damage and make them viable for transplantation.
In collaboration with Mayo Clinic William J. von Liebig Transplant Center, physicians and investigators in the Center for Regenerative Medicine are starting an ex vivo lung perfusion program, which is expected to be active by late 2012.
Recellularization of decellularized lungs. Toward a goal of on-demand production of patient-specific, transplant-ready lungs, Mayo Clinic researchers are studying lung decellularization and recellularization.
Lung decellularization involves removing all the cells from a donor lung, leaving behind just a tissue "scaffold" that can be recellularized — repopulated — with induced pluripotent stem (iPS) cells derived from a patient's own cells. Mayo researchers have recently had success generating a functioning lung suitable for transplantation by recellularizing a decellularized porcine lung.
Given these promising results in animal models, Mayo investigators are now working to recellularize human lungs. They're also populating decellularized matrix fragments with iPS cells to determine how iPS cells can optimally be made to differentiate into various types of lung cells.
Stem cell engineering. To better understand how to effectively and consistently produce patient-specific iPS cells for lung-related clinical applications, Mayo Clinic researchers are conducting a clinical trial in which they generate iPS cells from skin fibroblasts of people with various end-stage lung diseases.
With further research, investigators believe these iPS cells could be differentiated into patient-specific pulmonary epithelial cells and delivered back to the patient by way of cell therapy.