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Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study

BACKGROUND: Primary graft dysfunction (PGD) is a significant cause of early morbidity and mortality following lung transplantation. Improved organ preservation techniques will decrease ischemia-reperfusion injury (IRI) contributing to PGD. Adult bone marrow-derived adherent stem cells, including mes...

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Autores principales: La Francesca, Saverio, Ting, Anthony E, Sakamoto, Jason, Rhudy, Jessica, Bonenfant, Nicholas R, Borg, Zachary D, Cruz, Fernanda F, Goodwin, Meagan, Lehman, Nicholas A, Taggart, Jennifer M, Deans, Robert, Weiss, Daniel J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323223/
https://www.ncbi.nlm.nih.gov/pubmed/25671090
http://dx.doi.org/10.1186/2047-1440-3-19
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author La Francesca, Saverio
Ting, Anthony E
Sakamoto, Jason
Rhudy, Jessica
Bonenfant, Nicholas R
Borg, Zachary D
Cruz, Fernanda F
Goodwin, Meagan
Lehman, Nicholas A
Taggart, Jennifer M
Deans, Robert
Weiss, Daniel J
author_facet La Francesca, Saverio
Ting, Anthony E
Sakamoto, Jason
Rhudy, Jessica
Bonenfant, Nicholas R
Borg, Zachary D
Cruz, Fernanda F
Goodwin, Meagan
Lehman, Nicholas A
Taggart, Jennifer M
Deans, Robert
Weiss, Daniel J
author_sort La Francesca, Saverio
collection PubMed
description BACKGROUND: Primary graft dysfunction (PGD) is a significant cause of early morbidity and mortality following lung transplantation. Improved organ preservation techniques will decrease ischemia-reperfusion injury (IRI) contributing to PGD. Adult bone marrow-derived adherent stem cells, including mesenchymal stromal (stem) cells (MSCs) and multipotent adult progenitor cells (MAPCs), have potent anti-inflammatory actions, and we thus postulated that intratracheal MAPC administration during donor lung processing would decrease IRI. The goal of the study was therefore to determine if intratracheal MAPC instillation would decrease lung injury and inflammation in an ex vivo human lung explant model of prolonged cold storage and subsequent reperfusion. METHODS: Four donor lungs not utilized for transplant underwent 8 h of cold storage (4°C). Following rewarming for approximately 30 min, non-HLA-matched allogeneic MAPCs (1 × 10(7) MAPCs/lung) were bronchoscopically instilled into the left lower lobe (LLL) and vehicle comparably instilled into the right lower lobe (RLL). The lungs were then perfused and mechanically ventilated for 4 h and subsequently assessed for histologic injury and for inflammatory markers in bronchoalveolar lavage fluid (BALF) and lung tissue. RESULTS: All LLLs consistently demonstrated a significant decrease in histologic and BALF inflammation compared to vehicle-treated RLLs. CONCLUSIONS: These initial pilot studies suggest that use of non-HLA-matched allogeneic MAPCs during donor lung processing can decrease markers of cold ischemia-induced lung injury. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2047-1440-3-19) contains supplementary material, which is available to authorized users.
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spelling pubmed-43232232015-02-11 Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study La Francesca, Saverio Ting, Anthony E Sakamoto, Jason Rhudy, Jessica Bonenfant, Nicholas R Borg, Zachary D Cruz, Fernanda F Goodwin, Meagan Lehman, Nicholas A Taggart, Jennifer M Deans, Robert Weiss, Daniel J Transplant Res Research BACKGROUND: Primary graft dysfunction (PGD) is a significant cause of early morbidity and mortality following lung transplantation. Improved organ preservation techniques will decrease ischemia-reperfusion injury (IRI) contributing to PGD. Adult bone marrow-derived adherent stem cells, including mesenchymal stromal (stem) cells (MSCs) and multipotent adult progenitor cells (MAPCs), have potent anti-inflammatory actions, and we thus postulated that intratracheal MAPC administration during donor lung processing would decrease IRI. The goal of the study was therefore to determine if intratracheal MAPC instillation would decrease lung injury and inflammation in an ex vivo human lung explant model of prolonged cold storage and subsequent reperfusion. METHODS: Four donor lungs not utilized for transplant underwent 8 h of cold storage (4°C). Following rewarming for approximately 30 min, non-HLA-matched allogeneic MAPCs (1 × 10(7) MAPCs/lung) were bronchoscopically instilled into the left lower lobe (LLL) and vehicle comparably instilled into the right lower lobe (RLL). The lungs were then perfused and mechanically ventilated for 4 h and subsequently assessed for histologic injury and for inflammatory markers in bronchoalveolar lavage fluid (BALF) and lung tissue. RESULTS: All LLLs consistently demonstrated a significant decrease in histologic and BALF inflammation compared to vehicle-treated RLLs. CONCLUSIONS: These initial pilot studies suggest that use of non-HLA-matched allogeneic MAPCs during donor lung processing can decrease markers of cold ischemia-induced lung injury. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2047-1440-3-19) contains supplementary material, which is available to authorized users. BioMed Central 2014-11-01 /pmc/articles/PMC4323223/ /pubmed/25671090 http://dx.doi.org/10.1186/2047-1440-3-19 Text en © La Francesca et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
La Francesca, Saverio
Ting, Anthony E
Sakamoto, Jason
Rhudy, Jessica
Bonenfant, Nicholas R
Borg, Zachary D
Cruz, Fernanda F
Goodwin, Meagan
Lehman, Nicholas A
Taggart, Jennifer M
Deans, Robert
Weiss, Daniel J
Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study
title Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study
title_full Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study
title_fullStr Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study
title_full_unstemmed Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study
title_short Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study
title_sort multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323223/
https://www.ncbi.nlm.nih.gov/pubmed/25671090
http://dx.doi.org/10.1186/2047-1440-3-19
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