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Xenotransplantation of Mitochondria : A Novel Strategy to Alleviate Ischemia-Reperfusion Injury during Ex Vivo Lung Perfusion

Bechet, Nicholas B LU ; Celik, Aybuke LU ; Mittendorfer, Margareta LU ; Wang, Qi LU ; Huzevka, Tibor LU ; Kjellberg, Gunilla ; Boden, Embla LU ; Hirdman, Gabriel LU ; Pierre, Leif LU and Niroomand, Anna LU , et al. (2024) In The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
Abstract

Ischemia-reperfusion injury (IRI) plays a crucial role in the development of primary graft dysfunction (PGD) following lung transplantation. A promising novel approach to optimize donor organs before transplantation and reduce the incidence of PGD is mitochondrial transplantation. In this study, we explored the delivery of isolated mitochondria in 4 hour ex vivo lung perfusion (EVLP) before transplantation as a means to mitigate IRI. To provide a fresh and viable source of mitochondria, as well as to streamline the workflow without the need for donor muscle biopsies, we investigated the impact of autologous, allogeneic and xenogeneic mitochondrial transplantation. In the xenogeneic settings, isolated mitochondria from mouse liver were... (More)

Ischemia-reperfusion injury (IRI) plays a crucial role in the development of primary graft dysfunction (PGD) following lung transplantation. A promising novel approach to optimize donor organs before transplantation and reduce the incidence of PGD is mitochondrial transplantation. In this study, we explored the delivery of isolated mitochondria in 4 hour ex vivo lung perfusion (EVLP) before transplantation as a means to mitigate IRI. To provide a fresh and viable source of mitochondria, as well as to streamline the workflow without the need for donor muscle biopsies, we investigated the impact of autologous, allogeneic and xenogeneic mitochondrial transplantation. In the xenogeneic settings, isolated mitochondria from mouse liver were utilized while autologous and allogeneic sources came from pig skeletal muscle biopsies. Treatment with mitochondrial transplantation increased the P/F ratio and reduced pulmonary peak pressure of the lungs during EVLP, compared to lungs without any mitochondrial transplantation, indicating IRI mitigation. Extensive investigations using advanced light and scanning electron microscopy did not reveal evidence of acute rejection in any of the groups, indicating safe xenotransplantation of mitochondria. Future work is needed to further explore this novel therapy for combating IRI in lung transplantation, where xenotransplantation of mitochondria may serve as a fresh, viable source to reduce IRI.

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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:39536924
  • scopus:85210965046
ISSN
1557-3117
DOI
10.1016/j.healun.2024.10.033
language
English
LU publication?
yes
additional info
Copyright © 2024. Published by Elsevier Inc.
id
e5b017b2-ad15-4715-8805-3c1710fb347b
date added to LUP
2024-11-14 16:15:33
date last changed
2025-07-14 18:29:43
@article{e5b017b2-ad15-4715-8805-3c1710fb347b,
  abstract     = {{<p>Ischemia-reperfusion injury (IRI) plays a crucial role in the development of primary graft dysfunction (PGD) following lung transplantation. A promising novel approach to optimize donor organs before transplantation and reduce the incidence of PGD is mitochondrial transplantation. In this study, we explored the delivery of isolated mitochondria in 4 hour ex vivo lung perfusion (EVLP) before transplantation as a means to mitigate IRI. To provide a fresh and viable source of mitochondria, as well as to streamline the workflow without the need for donor muscle biopsies, we investigated the impact of autologous, allogeneic and xenogeneic mitochondrial transplantation. In the xenogeneic settings, isolated mitochondria from mouse liver were utilized while autologous and allogeneic sources came from pig skeletal muscle biopsies. Treatment with mitochondrial transplantation increased the P/F ratio and reduced pulmonary peak pressure of the lungs during EVLP, compared to lungs without any mitochondrial transplantation, indicating IRI mitigation. Extensive investigations using advanced light and scanning electron microscopy did not reveal evidence of acute rejection in any of the groups, indicating safe xenotransplantation of mitochondria. Future work is needed to further explore this novel therapy for combating IRI in lung transplantation, where xenotransplantation of mitochondria may serve as a fresh, viable source to reduce IRI.</p>}},
  author       = {{Bechet, Nicholas B and Celik, Aybuke and Mittendorfer, Margareta and Wang, Qi and Huzevka, Tibor and Kjellberg, Gunilla and Boden, Embla and Hirdman, Gabriel and Pierre, Leif and Niroomand, Anna and Olm, Franziska and McCully, James D and Lindstedt, Sandra}},
  issn         = {{1557-3117}},
  language     = {{eng}},
  month        = {{11}},
  publisher    = {{Elsevier}},
  series       = {{The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}},
  title        = {{Xenotransplantation of Mitochondria : A Novel Strategy to Alleviate Ischemia-Reperfusion Injury during Ex Vivo Lung Perfusion}},
  url          = {{http://dx.doi.org/10.1016/j.healun.2024.10.033}},
  doi          = {{10.1016/j.healun.2024.10.033}},
  year         = {{2024}},
}