Mesenchymal stromal cell therapy during ex vivo lung perfusion ameliorates ischemia-reperfusion injury in lung transplantation
| Autor: | David M. Hwang, Thomas K. Waddell, Akihiro Ohsumi, R. Coutinho, Shaf Keshavjee, John E. Davies, Pierre Mordant, Tereza Martinu, M. Pipkin, Stephen C. Juvet, Tomohito Saito, Manyin Chen, L. Caldarone, Marcelo Cypel, Mingyao Liu, Y. Watanabe, T. Kanou, Rohin K. Iyer, D. Nakajima, Ryan Lam |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Male Pathology medicine.medical_specialty Swine medicine.medical_treatment Cold storage Lung injury Mesenchymal Stem Cell Transplantation 03 medical and health sciences Random Allocation 0302 clinical medicine medicine Lung transplantation Animals Lung Transplantation business.industry Mesenchymal stem cell medicine.disease Perfusion Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Reperfusion Injury Surgery Hepatocyte growth factor Cardiology and Cardiovascular Medicine business Reperfusion injury medicine.drug Lung Transplantation |
| Zdroj: | The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 38(11) |
| ISSN: | 1557-3117 |
| Popis: | BACKGROUND The application of mesenchymal stromal cell (MSC)–based therapy during ex vivo lung perfusion (EVLP) could repair injured donor lungs before transplantation. The aim of this study was to determine the efficacy of MSC therapy performed during EVLP on ischemia-reperfusion injury using a pig lung transplant model. METHODS Following 24 hours of cold storage, pig lungs were randomly assigned to 2 groups (n = 6 each), the control group without MSC vs the MSC group, where 5 × 106 cells/kg MSCs were delivered through the pulmonary artery during EVLP. After 12 hours of EVLP, followed by a 1-hour second cold preservation period, the left lung was transplanted and reperfused for 4 hours. RESULTS EVLP perfusate hepatocyte growth factor (HGF) level at 12 hours was significantly elevated in the MSC group compared with the control and was associated with a significant decrease in cell death markers, cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling–positive cells, in the MSC group. The MSC group showed significantly lower interleukin (IL)-18 and interferon gamma levels and a significantly higher IL-4 level in lung tissue at 12 hours of EVLP than the control group. After transplantation, the MSC group showed a significant increase in lung tissue HGF level compared with the control group, associated with a significantly reduced lung tissue wet-to-dry weight ratio. Lung tissue tumor necrosis factor-α level and pathological acute lung injury score were significantly lower in the MSC group than the control group. CONCLUSIONS The administration of MSCs ameliorated ischemic injury in donor lungs during EVLP and attenuated the subsequent ischemia-reperfusion injury after transplantation. |
| Databáze: | OpenAIRE |
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