Mesenchymal Stem Cell Therapy Facilitates Donor Lung Preservation by Reducing Oxidative Damage during Ischemia
Lung transplantation is a lifesaving therapy for people living with severe, life-threatening lung disease. The high mortality rate among patients awaiting transplantation is mainly due to the low percentage of lungs that are deemed acceptable for implantation. Thus, the current shortage of lung dono...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/8089215 |
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| author | Natalia Pacienza Diego Santa-Cruz Ricardo Malvicini Oscar Robledo Gastón Lemus-Larralde Alejandro Bertolotti Martín Marcos Gustavo Yannarelli |
| author_facet | Natalia Pacienza Diego Santa-Cruz Ricardo Malvicini Oscar Robledo Gastón Lemus-Larralde Alejandro Bertolotti Martín Marcos Gustavo Yannarelli |
| author_sort | Natalia Pacienza |
| collection | DOAJ |
| description | Lung transplantation is a lifesaving therapy for people living with severe, life-threatening lung disease. The high mortality rate among patients awaiting transplantation is mainly due to the low percentage of lungs that are deemed acceptable for implantation. Thus, the current shortage of lung donors may be significantly reduced by implementing different therapeutic strategies which facilitate both organ preservation and recovery. Here, we studied whether the anti-inflammatory effect of human umbilical cord-derived mesenchymal stem cells (HUCPVCs) increases lung availability by improving organ preservation. We developed a lung preservation rat model that mimics the different stages by which donor organs must undergo before implantation. The therapeutic schema was as follows: cardiac arrest, warm ischemia (2 h at room temperature), cold ischemia (1.5 h at 4°C, with Perfadex), and normothermic lung perfusion with ventilation (Steen solution, 1 h). After 1 h of warm ischemia, HUCPVCs (1×106 cells) or vehicle was infused via the pulmonary artery. Physiologic data (pressure-volume curves) were acquired right after the cardiac arrest and at the end of the perfusion. Interestingly, although lung edema did not change among groups, lung compliance dropped to 34% in the HUCPVC-treated group, while the vehicle group showed a stronger reduction (69%, p<0.0001). Histologic assessment demonstrated less overall inflammation in the HUCPVC-treated lungs. In addition, MPO activity, a neutrophil marker, was reduced by 41% compared with vehicle (p<0.01). MSC therapy significantly decreased tissue oxidative damage by controlling reactive oxygen species production. Accordingly, catalase and superoxide dismutase enzyme activities remained at baseline levels. In conclusion, these results demonstrate that the anti-inflammatory effect of MSCs protects donor lungs against ischemic injury and postulates MSC therapy as a novel tool for organ preservation. |
| format | Article |
| id | doaj-art-3fe9cd329040469bbe73f47d9e66badb |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-3fe9cd329040469bbe73f47d9e66badb2025-08-20T03:55:36ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/80892158089215Mesenchymal Stem Cell Therapy Facilitates Donor Lung Preservation by Reducing Oxidative Damage during IschemiaNatalia Pacienza0Diego Santa-Cruz1Ricardo Malvicini2Oscar Robledo3Gastón Lemus-Larralde4Alejandro Bertolotti5Martín Marcos6Gustavo Yannarelli7Laboratorio de Regulación Génica y Células Madre, Instituto de Medicina Traslacional, Trasplante y Bioingeniería (IMeTTyB), Universidad Favaloro-CONICET, Solís 453, CABA (1078), Buenos Aires, ArgentinaLaboratorio de Regulación Génica y Células Madre, Instituto de Medicina Traslacional, Trasplante y Bioingeniería (IMeTTyB), Universidad Favaloro-CONICET, Solís 453, CABA (1078), Buenos Aires, ArgentinaLaboratorio de Regulación Génica y Células Madre, Instituto de Medicina Traslacional, Trasplante y Bioingeniería (IMeTTyB), Universidad Favaloro-CONICET, Solís 453, CABA (1078), Buenos Aires, ArgentinaDepartamento de Cirugía, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, Calle 60 y 118, La Plata (1900), Buenos Aires, ArgentinaDepartamento de Cirugía, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, Calle 60 y 118, La Plata (1900), Buenos Aires, ArgentinaDepartamento de Cirugía Cardiovascular y Torácica, Hospital Universitario Fundación Favaloro, Av. Belgrano 1746, CABA (1039), Buenos Aires, ArgentinaDepartamento de Cirugía, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, Calle 60 y 118, La Plata (1900), Buenos Aires, ArgentinaLaboratorio de Regulación Génica y Células Madre, Instituto de Medicina Traslacional, Trasplante y Bioingeniería (IMeTTyB), Universidad Favaloro-CONICET, Solís 453, CABA (1078), Buenos Aires, ArgentinaLung transplantation is a lifesaving therapy for people living with severe, life-threatening lung disease. The high mortality rate among patients awaiting transplantation is mainly due to the low percentage of lungs that are deemed acceptable for implantation. Thus, the current shortage of lung donors may be significantly reduced by implementing different therapeutic strategies which facilitate both organ preservation and recovery. Here, we studied whether the anti-inflammatory effect of human umbilical cord-derived mesenchymal stem cells (HUCPVCs) increases lung availability by improving organ preservation. We developed a lung preservation rat model that mimics the different stages by which donor organs must undergo before implantation. The therapeutic schema was as follows: cardiac arrest, warm ischemia (2 h at room temperature), cold ischemia (1.5 h at 4°C, with Perfadex), and normothermic lung perfusion with ventilation (Steen solution, 1 h). After 1 h of warm ischemia, HUCPVCs (1×106 cells) or vehicle was infused via the pulmonary artery. Physiologic data (pressure-volume curves) were acquired right after the cardiac arrest and at the end of the perfusion. Interestingly, although lung edema did not change among groups, lung compliance dropped to 34% in the HUCPVC-treated group, while the vehicle group showed a stronger reduction (69%, p<0.0001). Histologic assessment demonstrated less overall inflammation in the HUCPVC-treated lungs. In addition, MPO activity, a neutrophil marker, was reduced by 41% compared with vehicle (p<0.01). MSC therapy significantly decreased tissue oxidative damage by controlling reactive oxygen species production. Accordingly, catalase and superoxide dismutase enzyme activities remained at baseline levels. In conclusion, these results demonstrate that the anti-inflammatory effect of MSCs protects donor lungs against ischemic injury and postulates MSC therapy as a novel tool for organ preservation.http://dx.doi.org/10.1155/2019/8089215 |
| spellingShingle | Natalia Pacienza Diego Santa-Cruz Ricardo Malvicini Oscar Robledo Gastón Lemus-Larralde Alejandro Bertolotti Martín Marcos Gustavo Yannarelli Mesenchymal Stem Cell Therapy Facilitates Donor Lung Preservation by Reducing Oxidative Damage during Ischemia Stem Cells International |
| title | Mesenchymal Stem Cell Therapy Facilitates Donor Lung Preservation by Reducing Oxidative Damage during Ischemia |
| title_full | Mesenchymal Stem Cell Therapy Facilitates Donor Lung Preservation by Reducing Oxidative Damage during Ischemia |
| title_fullStr | Mesenchymal Stem Cell Therapy Facilitates Donor Lung Preservation by Reducing Oxidative Damage during Ischemia |
| title_full_unstemmed | Mesenchymal Stem Cell Therapy Facilitates Donor Lung Preservation by Reducing Oxidative Damage during Ischemia |
| title_short | Mesenchymal Stem Cell Therapy Facilitates Donor Lung Preservation by Reducing Oxidative Damage during Ischemia |
| title_sort | mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia |
| url | http://dx.doi.org/10.1155/2019/8089215 |
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