In a recent study in Stem Cells Translational Medicine, a team of researchers at Mayo Clinic looked at the safety and feasibility of using stem cells to treat a condition that can devastate lung transplant patients. The disease itself is called bronchiolitis obliterans syndrome, or BOS, and involves inflammation and scarring in the smallest branches of airways that can cause significant discomfort and shortness of breath. BOS can lead to the need for a re-transplant, or even be fatal. Improving the treatment of BOS, in particular by using stem cells to mobilize the immune system and reduce inflammation, may improve the long-term outcomes of lung transplants.
The study looked at the safety of using an infusion of bone-marrow derived stem cells—known as mesenchymal stem cells—that all came from one healthy donor. The recipients of the cells were patients with BOS who hadn’t gotten better with medical treatment and weren't candidates for another transplant. “We found that the acute infusion of mesenchymal stem cells didn’t induce any changes in vital signs or produce any worsening of lung function, ventilation or oxygenation,” says lead author pulmonologist Cesar Keller, M.D. What’s more, no adverse effects turned up even a year after the infusion. The study also shed light on the dosing of stem cells (patients received 1, 2, or 4 million stem cells/kg), and researchers were surprised to note the lowest dose of cells seemed to work best.
Knowing that this therapy is feasible and safe opens the door for future studies testing whether stem cells (either derived from and returned to a patient or obtained from a healthy donor) can treat some of the long and short term complications of lung transplant. Stem cells might reduce the need for heavy immunosuppressive drugs, which often lead to patients' infections, and may even reduce transplant rejection. The studies are still at an early stage, and larger Phase II studies are necessary to test how stem cell therapy might work as a potential early immunomodulatory technique or as rescue therapy for lung transplant recipients with acute or chronic rejection.
But another important aspect of the study was its scrutiny of how the cells were transported to the patients. Detailing the steps of manufacturing, freezing and delivering the cells, the study ascertained the stem cells were viable and sterile at the end of their journey. “Our results showed that indeed the logistics of preparing, transporting, and infusing cells was feasible and safe,” Dr. Keller says. These findings provide important information as Mayo Clinic takes pioneering steps as the Food and Drug Administration has recently allowed for an automated stem cell manufacturing platform on the campus in Jacksonville, Florida. “Our completed study opens opportunities for subsequent studies of stem cells in lung transplant recipients or recipients of other solid organs,” Dr. Keller adds. The study also ascertained the feasibility of shipping viable stem cells for clinical studies in Rochester, Minnesota and Scottsdale, Arizona.
For the latest on regenerative medicine at Mayo Clinic, visit the Center for Regenerative Medicine blog.