Xenotransplantation of Mitochondria : A Novel Strategy to Alleviate Ischemia-Reperfusion Injury during Ex Vivo Lung Perfusion
(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.
(Less)
- author
- organization
-
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- WCMM-Wallenberg Centre for Molecular Medicine
- Stem Cell Center
- Thoracic Surgery
- LUCC: Lund University Cancer Centre
- DCD transplantation of lungs (research group)
- Clinical and experimental lung transplantation (research group)
- NPWT technology (research group)
- publishing date
- 2024-11-11
- 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: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}}, }