Mesenchymal Stem Cells Attenuates Ischemia Reperfusion Injury after Orthotopic Lung Transplantation in a Mouse Model

Abstract

Purpose Mesenchymal stem cells (MSCs), multipotent mesenchymal stromal cells, have been shown to possess immunomodulatory and antiinflammatory properties. We hypothesized that MSCs may attenuate ischemia reperfusion injury after lung transplantation in mice. Methods and Materials C57BL/6 lungs were stored for 18 hours in low-potassium dextran glucose solution at 4°C prior to transplantation. The left lung grafts were orthotopically transplanted into C57BL/6 mice. A frozen vial of human MSCs (isolated from healthy male, courtesy of Dr. Darwin Prockop, Texas AM 1.095 vs 1.965 mg/ml, p=0.037, cell count; 0.61x10^5 vs 1.09x10^5 cells, p=0.011). IL-1β, IL17A and TNFα levels in BALF showed a trend toward a decrease in MSCs administered mice compared with PBS administered mice (IL-1β; 26.6 vs 38.7 pg/ml, p=0.13, IL17A; 284 vs 655 pg/ml, p=0.097, TNFα; 234 vs 500 pg/ml, p=0.073). Human MSCs were found in the lung graft 6 hours after lung transplantation by immunohistochemistry against human HLA class I. Conclusions MSCs attenuated ischemia reperfusion injury, which was accompanied by a trend toward decreased levels of proinflammatory cytokines in the graft after lung transplantation in a mouse model.