Fresh and Cryopreserved Human Umbilical-Cord-Derived Mesenchymal Stromal Cells Attenuate Injury and Enhance Resolution and Repair following Ventilation-Induced Lung Injury.


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
27 Nov 2021
Historique:
received: 22 10 2021
revised: 25 11 2021
accepted: 26 11 2021
entrez: 10 12 2021
pubmed: 11 12 2021
medline: 27 1 2022
Statut: epublish

Résumé

Ventilator-induced lung injury (VILI) frequently worsens acute respiratory distress syndrome (ARDS) severity. Human mesenchymal stem/stromal cells (MSCs) offer considerable therapeutic promise, but the key impediments of clinical translation stem from limitations due to cell source and availability, and concerns regarding the loss of efficacy following cryopreservation. These experiments compared the efficacy of umbilical-cord-derived MSCs (UC-MSCs), a readily available and homogenous tissue source, to the previously more widely utilised bone-marrow-derived MSCs (BM-MSCs). We assessed their capacity to limit inflammation, resolve injury and enhance repair in relevant lung mechanical stretch models, and the impact of cryopreservation on therapeutic efficacy. In Conditioned medium from BM-MSCs and UC-MSCs comparably decreased stretch-induced pulmonary epithelial inflammation and cell death. BM-MSCs and UC-MSCs comparably enhanced wound resolution. In animals subjected to VILI, both fresh BM-MSCs and UC-MSCs enhanced injury resolution and repair, while cryopreserved UC-MSCs comparably retained their efficacy. Cryopreserved UC-MSCs can reduce stretch-induced inflammation and cell death, enhance wound resolution, and enhance injury resolution and repair following VILI. Cryopreserved UC-MSCs represent a more abundant, cost-efficient, less variable and equally efficacious source of therapeutic MSC product.

Sections du résumé

BACKGROUND BACKGROUND
Ventilator-induced lung injury (VILI) frequently worsens acute respiratory distress syndrome (ARDS) severity. Human mesenchymal stem/stromal cells (MSCs) offer considerable therapeutic promise, but the key impediments of clinical translation stem from limitations due to cell source and availability, and concerns regarding the loss of efficacy following cryopreservation. These experiments compared the efficacy of umbilical-cord-derived MSCs (UC-MSCs), a readily available and homogenous tissue source, to the previously more widely utilised bone-marrow-derived MSCs (BM-MSCs). We assessed their capacity to limit inflammation, resolve injury and enhance repair in relevant lung mechanical stretch models, and the impact of cryopreservation on therapeutic efficacy.
METHODS METHODS
In
RESULTS RESULTS
Conditioned medium from BM-MSCs and UC-MSCs comparably decreased stretch-induced pulmonary epithelial inflammation and cell death. BM-MSCs and UC-MSCs comparably enhanced wound resolution. In animals subjected to VILI, both fresh BM-MSCs and UC-MSCs enhanced injury resolution and repair, while cryopreserved UC-MSCs comparably retained their efficacy.
CONCLUSIONS CONCLUSIONS
Cryopreserved UC-MSCs can reduce stretch-induced inflammation and cell death, enhance wound resolution, and enhance injury resolution and repair following VILI. Cryopreserved UC-MSCs represent a more abundant, cost-efficient, less variable and equally efficacious source of therapeutic MSC product.

Identifiants

pubmed: 34884645
pii: ijms222312842
doi: 10.3390/ijms222312842
pmc: PMC8657992
pii:
doi:

Substances chimiques

Culture Media, Conditioned 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : European Research Council
ID : ERC-2007-StG 207777
Pays : International
Organisme : Science Foundation Ireland
ID : 16/FRL/3845
Pays : Ireland
Organisme : Health Research Board
ID : HRA-POR-2015-1099
Pays : Ireland
Organisme : Science Foundation Ireland
ID : 14/TIDA/2291
Pays : Ireland

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Auteurs

Shahd Horie (S)

Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, H91 TK33 Galway, Ireland.
Regenerative Medicine Institute (REMEDI), CÚRAM Centre for Research in Medical Devices, National University of Ireland Galway, Biomedical Sciences Building, H91 TK33 Galway, Ireland.

Hector Gonzalez (H)

Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, H91 TK33 Galway, Ireland.
Regenerative Medicine Institute (REMEDI), CÚRAM Centre for Research in Medical Devices, National University of Ireland Galway, Biomedical Sciences Building, H91 TK33 Galway, Ireland.

Jack Brady (J)

Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, H91 TK33 Galway, Ireland.
Regenerative Medicine Institute (REMEDI), CÚRAM Centre for Research in Medical Devices, National University of Ireland Galway, Biomedical Sciences Building, H91 TK33 Galway, Ireland.

James Devaney (J)

Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, H91 TK33 Galway, Ireland.
Regenerative Medicine Institute (REMEDI), CÚRAM Centre for Research in Medical Devices, National University of Ireland Galway, Biomedical Sciences Building, H91 TK33 Galway, Ireland.

Michael Scully (M)

Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, H91 TK33 Galway, Ireland.
Medicine, School of Medicine, Clinical Sciences Institute, National University of Ireland, H91 TK33 Galway, Ireland.

Daniel O'Toole (D)

Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, H91 TK33 Galway, Ireland.
Regenerative Medicine Institute (REMEDI), CÚRAM Centre for Research in Medical Devices, National University of Ireland Galway, Biomedical Sciences Building, H91 TK33 Galway, Ireland.

John G Laffey (JG)

Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, H91 TK33 Galway, Ireland.
Regenerative Medicine Institute (REMEDI), CÚRAM Centre for Research in Medical Devices, National University of Ireland Galway, Biomedical Sciences Building, H91 TK33 Galway, Ireland.
Medicine, School of Medicine, Clinical Sciences Institute, National University of Ireland, H91 TK33 Galway, Ireland.
Department of Anaesthesia, Galway University Hospitals, SAOLTA University Health Group, H91 YR71 Galway, Ireland.

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