Lung transplants can be miracles that extend the lives of patients who might otherwise have died. But in a large percentage of transplant recipients, a new condition emerges with the new set of lungs: organ rejection.
Abba Zubair, a physician-researcher at the Mayo Clinic, sees patients with chronic transplant rejection often in his practice. “They are desperate,” he said. “Think about it like a perpetual asthmatic attack. It’s a horrible situation to see them in, especially those who are at the terminal end of their disease.”
Zubair is interested in how cells traffic around the body and modulate the local environments around them. Driven by that interest, he frequently collects from his patients a type of stem cell that has some unusual properties. The mesenchymal stem cells (MSCs) he collects can secrete cytokines and growth factors, and they can modulate the body’s immune responses, which other types of stem cells cannot do.
Abba Zubair is a stem cell researcher at the Mayo Clinic who studies stem cells and cell trafficking.
Credit: Mayo Clinic
Recently, Zubair connected his research interests with the desperate patients he sees in the clinic. In his new publication in Stem Cells Translational Medicine, Zubair described the safety of treating patients with chronic lung rejection with a single dose of MSCs (1).
Zubair and his team selected 13 patients for treatment because they had chronic lung allograft syndrome (CLAD), a group of related states stemming from transplant rejection that makes breathing difficult and can result in transplant failure and death (2). The team measured the volume of the patients’ breath, a proxy for lung capacity and function, for more than a year before the actual treatment. That volume across the entire group persistently dropped until the day of the treatment. The patients ranged in age from 36 to 74, had received single or double transplants, and were as far as a decade from the dates of their transplants. Zubair’s team infused the 13 patients with MSCs and tracked their progress for more than a year.
The MSCs halted that lung function decline. After the transfusion, none of the patients declined in the measured volume of their breath, and for several, lung function even improved. Perhaps most importantly for transplant recipients, all patients tolerated the transfusion well, even though the MSCs were derived from a donor.
“Traditionally lung transplant recipients haven't done as well as other organ transplant recipients,” said Shambhu Aryal, an internal medicine specialist and director of the lung transplant program at Inova Health Systems who was not involved in the research. “We tend to think of chronic rejection as something that's progressive and whatever damage is done is hard to reverse,” he said, concluding that the MSC’s ability to improve lung function in some cases is an exciting development.
More than half of patients who receive new lungs experience rejection. Patients must continuously take immunosuppressant drugs that ease rejection symptoms while making patients susceptible to infection. While medical advances have improved the one-year survival rate from 45 percent in 1990 to 83 percent in 2016, five-year survival for lung transplant recipients still hovers at around 50 percent (2). This could be due to frequent rates of rejection stemming from the lung’s unique position among common organ transplants. The lungs are continuously exposed to particulates and bacteria in the air, which can both cause irritation and stimulate the immune system to attack the lungs.
Despite the success of the treatment, how MSCs actually heal and stabilize breathing function in lung transplant patients isn’t yet clear. Stem cells could either heal tissue directly by differentiating into new lung tissue or by releasing anti-inflammatory and immunosuppressant molecules. A quirk of MSCs makes them particularly advantageous for lung transplants over other organ transplant recipients: MSCs frequently get trapped in the lungs after transfusion. This phenomenon, known as the “pulmonary first-pass effect,” makes them less useful for rejection in other organs, but almost tailor-made for the lungs.
“There is so much promise in regenerative therapies in the kind of work we’re doing,” Zubair said. “But we’re not there yet.”
References
- Erasmus, D. B. et al. Feasibility and Safety of Low-Dose Mesenchymal Stem Cell Infusion in Lung Transplant Recipients. Stem Cells Transl Med 11, 891–899 (2022).
- Gauthier, J. M., Hachem, R. R. & Kreisel, D. Update on Chronic Lung Allograft Dysfunction. Curr Transplant Rep 3, 185–191 (2016).
- Keller, C. A. et al. Feasibility, Safety, and Tolerance of Mesenchymal Stem Cell Therapy for Obstructive Chronic Lung Allograft Dysfunction. Stem Cells Transl Med 7, 161–167 (2018).
- Moyron-Quiroz, J. E. et al. Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity. Nat Med 10, 927–934 (2004).
