Ex vivo and in vivo immunomodulation in acute lung injury and lung transplantation
(2026) In Lund University, Faculty of Medicine Doctoral Dissertation Series- Abstract
- Lung transplantation (LTx) remains the only curative treatment for patients with end-stage lung disease, yet long-term outcomes remain inferior to those of other solid organ transplantations, with a 5-year survival below 70%. Major contributors to this limited outcome include primary graft dysfunction (PGD), the leading cause of early mortality, chronic lung allograft dysfunction (CLAD), and low utilization of available donor lungs. Currently, only about 20% of potential donor lungs are used for transplantation, as many are declined due to factors such as infection or inflammation, contusion, size mismatch, or aspiration. Aspiration of gastric contents can lead to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), a... (More)
- Lung transplantation (LTx) remains the only curative treatment for patients with end-stage lung disease, yet long-term outcomes remain inferior to those of other solid organ transplantations, with a 5-year survival below 70%. Major contributors to this limited outcome include primary graft dysfunction (PGD), the leading cause of early mortality, chronic lung allograft dysfunction (CLAD), and low utilization of available donor lungs. Currently, only about 20% of potential donor lungs are used for transplantation, as many are declined due to factors such as infection or inflammation, contusion, size mismatch, or aspiration. Aspiration of gastric contents can lead to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), a contributor to the development of PGD. Thus, strategies to both expand the donor pool and improve post-transplant outcomes are urgently needed.
Ex vivo lung perfusion (EVLP) has increased donor lung utilization by allowing functional assessment and short-term preservation of donor lungs outside the body. Apart from enabling lung ventilation and perfusion ex vivo, EVLP also provides a platform to test therapeutic interventions aimed at regenerating injured organs prior to transplantation. Targeting inflammatory pathways or promoting tissue repair during EVLP represents a promising strategy to rehabilitate marginal donor lungs.
This doctoral thesis investigated regenerative and immunomodulatory therapeutic strategies to restore donor lungs unsuitable for transplantation, with the goal of expanding the donor pool and improving post-transplant outcomes. In addition, the work aimed to increase the understanding of the molecular and immunological processes occurring during lung injury and lung transplantation and how these might be modulated by regenerative therapies. To address these objectives, several approaches were examined, including cytokine adsorption during lung transplantation in human patients, neutrophil extracellular trap removal during ex vivo lung perfusion, and mesenchymal stromal cell therapies to restore injured lungs and mitigate lung injury and graft dysfunction in porcine models. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8770aaf5-a66a-47de-aecc-b2b9334209e9
- author
- Mittendorfer, Margareta LU
- supervisor
- opponent
-
- Associate Professor Bello, Irene, Vall d'Hebron Hospital Universitari, Barcelona, Catalonia, Spain
- organization
- publishing date
- 2026
- type
- Thesis
- publication status
- published
- subject
- keywords
- lung transplantation, donor lung injury, ex vivo lung perfusion, primary graft dysfunction, cytokine adsorption, neutrophil extracellular traps, mesenchymal stromal cells, cell therapy
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2026:76
- pages
- 97 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Belfragesalen, BMC D15, Klinikgatan 32 i Lund. Join by Zoom: https://lu-se.zoom.us/j/62560851842
- defense date
- 2026-05-21 08:30:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-874-0
- language
- English
- LU publication?
- yes
- id
- 8770aaf5-a66a-47de-aecc-b2b9334209e9
- date added to LUP
- 2026-04-24 11:45:34
- date last changed
- 2026-05-05 14:19:23
@phdthesis{8770aaf5-a66a-47de-aecc-b2b9334209e9,
abstract = {{Lung transplantation (LTx) remains the only curative treatment for patients with end-stage lung disease, yet long-term outcomes remain inferior to those of other solid organ transplantations, with a 5-year survival below 70%. Major contributors to this limited outcome include primary graft dysfunction (PGD), the leading cause of early mortality, chronic lung allograft dysfunction (CLAD), and low utilization of available donor lungs. Currently, only about 20% of potential donor lungs are used for transplantation, as many are declined due to factors such as infection or inflammation, contusion, size mismatch, or aspiration. Aspiration of gastric contents can lead to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), a contributor to the development of PGD. Thus, strategies to both expand the donor pool and improve post-transplant outcomes are urgently needed.<br/>Ex vivo lung perfusion (EVLP) has increased donor lung utilization by allowing functional assessment and short-term preservation of donor lungs outside the body. Apart from enabling lung ventilation and perfusion ex vivo, EVLP also provides a platform to test therapeutic interventions aimed at regenerating injured organs prior to transplantation. Targeting inflammatory pathways or promoting tissue repair during EVLP represents a promising strategy to rehabilitate marginal donor lungs.<br/>This doctoral thesis investigated regenerative and immunomodulatory therapeutic strategies to restore donor lungs unsuitable for transplantation, with the goal of expanding the donor pool and improving post-transplant outcomes. In addition, the work aimed to increase the understanding of the molecular and immunological processes occurring during lung injury and lung transplantation and how these might be modulated by regenerative therapies. To address these objectives, several approaches were examined, including cytokine adsorption during lung transplantation in human patients, neutrophil extracellular trap removal during ex vivo lung perfusion, and mesenchymal stromal cell therapies to restore injured lungs and mitigate lung injury and graft dysfunction in porcine models.}},
author = {{Mittendorfer, Margareta}},
isbn = {{978-91-8021-874-0}},
issn = {{1652-8220}},
keywords = {{lung transplantation; donor lung injury; ex vivo lung perfusion; primary graft dysfunction; cytokine adsorption; neutrophil extracellular traps; mesenchymal stromal cells; cell therapy}},
language = {{eng}},
number = {{2026:76}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Ex vivo and in vivo immunomodulation in acute lung injury and lung transplantation}},
url = {{https://lup.lub.lu.se/search/files/248384406/Margareta_Mittendorfer_-_WEBB.pdf}},
year = {{2026}},
}