Background: Processes that activate the immune system during lung transplantation can lead to primary graft dysfunction (PGD) or allograft rejection.Methods: We analyzed cytokine expression profiles after reperfusion and allograft outcomes in a cohort of patients (n = 59) who underwent lung transplantation off‐pump (n = 26), with cardiopulmonary bypass (CPB; n = 18), or with extracorporeal membrane oxygenation (ECMO; n = 15). Peripheral blood was collected from patients at baseline and at 6 and 72 h after reperfusion. To adjust for clinical differences between groups, we utilized a linear mixed model with overlap weighting.Results: PGD3 was present at 48 or 72 h after reperfusion in 7.7% (2/26) of off‐pump cases, 20.0% (3/15) of ECMO cases, and 38.9% (7/18) of CPB cases (p = 0.04). The ECMO and CPB groups had greater reperfusion‐induced increases in MIP‐1B, IL‐6, IL‐8, IL‐9, IL1‐ra, TNF‐alpha, RANTES, eotaxin, IP‐10, and MCP‐1 levels than the off‐pump group. Cytokine expression profiles after reperfusion were not significantly different between ECMO and CPB groups.Conclusion: Our data suggest that, compared with an off‐pump approach, the intraoperative use of ECMO or CPB during lung transplantation is associated with greater reperfusion‐induced cytokine release and graft injury.

Ischemic heart disease, a leading cause of death worldwide, manifests clinically as myocardial infarction. Contemporary therapies using mesenchymal stromal cells (MSCs) and their derivative (exosomes, EXOs) were developed to decrease the progression of cell damage during ischemic injury. Laminin alpha 2 (LAMA2) is an important extracellular matrix protein of the heart. Here, we generated MSC-derived exosomes cultivated under LAMA2 coating to enhance human-induced pluripotent stem cell (hiPSC)-cardiomyocyte recognition of LAMA2-EXOs, thus, increasing cell protection during ischemia reoxygenation. We mapped the mRNA content of LAMA2 and gelatin-EXOs and identified 798 genes that were differentially expressed, including genes associated with cardiac muscle development and extracellular matrix organization. Cells were treated with LAMA2-EXOs 2 h before a 4 h ischemia period (1% O₂, 5% CO₂, glucose-free media). LAMA2-EXOs had a two-fold protective effect compared to non-treatment on plasma membrane integrity and the apoptosis activation pathway; after a 1.5 h recovery period (20% O₂, 5% CO₂, cardiomyocyte-enriched media), cardiomyocytes treated with LAMA2-EXOs showed faster recovery than did the control group. Although EXOs had a protective effect on endothelial cells, there was no LAMA2-enhanced protection on these cells. This is the first report of LAMA2-EXOs used to treat cardiomyocytes that underwent ischemia-reoxygenation injury. Overall, we showed that membrane-specific EXOs may help improve cardiomyocyte survival in treating ischemic cardiovascular disease.