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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Autores principales: Pacienza, Natalia, Santa Cruz, Diego, Malvicini, Ricardo, Robledo, Oscar Juan Alberto, Lemus Larralde, Gastón, Bertolotti, Alejandro, Marcos, Martín Alejandro, Yannarelli, Gustavo
Formato: Articulo
Lenguaje:Inglés
Publicado: 2019
Materias:
Ciencias Médicas
Veterinaria
lungs
transplantation
ischemia
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/107933
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6701419&blobtype=pdf
https://www.hindawi.com/journals/sci/2019/8089215/
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-107933
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Veterinaria
lungs
transplantation
ischemia
spellingShingle Ciencias Médicas
Veterinaria
lungs
transplantation
ischemia
Pacienza, Natalia
Santa Cruz, Diego
Malvicini, Ricardo
Robledo, Oscar Juan Alberto
Lemus Larralde, Gastón
Bertolotti, Alejandro
Marcos, Martín Alejandro
Yannarelli, Gustavo
Mesenchymal Stem Cell Therapy Facilitates Donor Lung Preservation by Reducing Oxidative Damage during Ischemia
topic_facet Ciencias Médicas
Veterinaria
lungs
transplantation
ischemia
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 × 10<sup>6</sup> 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 Articulo
Articulo
author Pacienza, Natalia
Santa Cruz, Diego
Malvicini, Ricardo
Robledo, Oscar Juan Alberto
Lemus Larralde, Gastón
Bertolotti, Alejandro
Marcos, Martín Alejandro
Yannarelli, Gustavo
author_facet Pacienza, Natalia
Santa Cruz, Diego
Malvicini, Ricardo
Robledo, Oscar Juan Alberto
Lemus Larralde, Gastón
Bertolotti, Alejandro
Marcos, Martín Alejandro
Yannarelli, Gustavo
author_sort Pacienza, Natalia
title 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_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_sort mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia
publishDate 2019
url http://sedici.unlp.edu.ar/handle/10915/107933
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6701419&blobtype=pdf
https://www.hindawi.com/journals/sci/2019/8089215/
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