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Amniotic fluid derived mesenchymal stem cells reduce inflammation and improve lung function following transplantation in a porcine model

Edström, Dag LU ; Niroomand, Anna LU ; Stenlo, Martin LU ; Broberg, Ellen LU ; Hirdman, Gabriel LU ; Ghaidan, Haider LU orcid ; Hyllén, Snejana LU ; Pierre, Leif LU ; Olm, Franziska LU orcid and Lindstedt, Sandra LU (2024) In The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
Abstract

BACKGROUND: Lung transplantation is hindered by low donor lung utilization rates. Infectious complications are reasons to decline donor grafts due to fear of post-transplant primary graft dysfunction. Mesenchymal stem cells are a promising therapy currently investigated in treating lung injury. Full-term amniotic fluid-derived lung-specific mesenchymal stem cell treatment may regenerate damaged lungs. These cells have previously demonstrated inflammatory mediation in other respiratory diseases, and we hypothesized that treatment would improve donor lung quality and post-operative outcomes.

METHODS: In a transplantation model, donor pigs were stratified to either the treated or the non-treated group. Acute respiratory distress... (More)

BACKGROUND: Lung transplantation is hindered by low donor lung utilization rates. Infectious complications are reasons to decline donor grafts due to fear of post-transplant primary graft dysfunction. Mesenchymal stem cells are a promising therapy currently investigated in treating lung injury. Full-term amniotic fluid-derived lung-specific mesenchymal stem cell treatment may regenerate damaged lungs. These cells have previously demonstrated inflammatory mediation in other respiratory diseases, and we hypothesized that treatment would improve donor lung quality and post-operative outcomes.

METHODS: In a transplantation model, donor pigs were stratified to either the treated or the non-treated group. Acute respiratory distress syndrome was induced in donor pigs and harvested lungs were placed on ex vivo lung perfusion before transplantation. Treatment consisted of three doses of 2x10
6 cells/kg: one during ex vivo lung perfusion and two after transplantation. Donors and recipients were assessed on clinically relevant parameters and recipients were followed for 3 days before evaluation for primary graft dysfunction (PGD).

RESULTS: Repeated injection of the cell treatment showed reductions in inflammation seen through lowered immune cell counts, reduced histology signs of inflammation, and decreased cytokines in the plasma and bronchoalveolar lavage fluid. Treated recipients showed improved pulmonary function, including increased PaO
2/FiO
2 ratios and reduced incidence of PGD.

CONCLUSIONS: Repeated injection of lung-specific cell treatment during EVLP and post-transplant was associated with improved function of previously damaged lungs. Cell treatment may be considered as a potential therapy to increase the number of lungs available for transplantation and the improvement of post-operative outcomes.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
publisher
Elsevier
external identifiers
  • pmid:39182800
ISSN
1557-3117
DOI
10.1016/j.healun.2024.08.014
language
English
LU publication?
yes
additional info
Copyright © 2024. Published by Elsevier Inc.
id
67a2ce90-dbd2-4cea-a546-327cf5f7c33d
date added to LUP
2024-08-29 14:16:43
date last changed
2024-08-29 15:45:32
@article{67a2ce90-dbd2-4cea-a546-327cf5f7c33d,
  abstract     = {{<p>BACKGROUND: Lung transplantation is hindered by low donor lung utilization rates. Infectious complications are reasons to decline donor grafts due to fear of post-transplant primary graft dysfunction. Mesenchymal stem cells are a promising therapy currently investigated in treating lung injury. Full-term amniotic fluid-derived lung-specific mesenchymal stem cell treatment may regenerate damaged lungs. These cells have previously demonstrated inflammatory mediation in other respiratory diseases, and we hypothesized that treatment would improve donor lung quality and post-operative outcomes.</p><p>METHODS: In a transplantation model, donor pigs were stratified to either the treated or the non-treated group. Acute respiratory distress syndrome was induced in donor pigs and harvested lungs were placed on ex vivo lung perfusion before transplantation. Treatment consisted of three doses of 2x10<br>
 6 cells/kg: one during ex vivo lung perfusion and two after transplantation. Donors and recipients were assessed on clinically relevant parameters and recipients were followed for 3 days before evaluation for primary graft dysfunction (PGD).<br>
 </p><p>RESULTS: Repeated injection of the cell treatment showed reductions in inflammation seen through lowered immune cell counts, reduced histology signs of inflammation, and decreased cytokines in the plasma and bronchoalveolar lavage fluid. Treated recipients showed improved pulmonary function, including increased PaO<br>
 2/FiO<br>
 2 ratios and reduced incidence of PGD.<br>
 </p><p>CONCLUSIONS: Repeated injection of lung-specific cell treatment during EVLP and post-transplant was associated with improved function of previously damaged lungs. Cell treatment may be considered as a potential therapy to increase the number of lungs available for transplantation and the improvement of post-operative outcomes.</p>}},
  author       = {{Edström, Dag and Niroomand, Anna and Stenlo, Martin and Broberg, Ellen and Hirdman, Gabriel and Ghaidan, Haider and Hyllén, Snejana and Pierre, Leif and Olm, Franziska and Lindstedt, Sandra}},
  issn         = {{1557-3117}},
  language     = {{eng}},
  month        = {{08}},
  publisher    = {{Elsevier}},
  series       = {{The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}},
  title        = {{Amniotic fluid derived mesenchymal stem cells reduce inflammation and improve lung function following transplantation in a porcine model}},
  url          = {{http://dx.doi.org/10.1016/j.healun.2024.08.014}},
  doi          = {{10.1016/j.healun.2024.08.014}},
  year         = {{2024}},
}