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Building Basic and Clinical Research Around Lung Transplantation

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Contemporary Lung Transplantation

Abstract

Over the years, allogeneic lung transplantation (LTx) has become a promising therapy for end-stage lung diseases patients. Unfortunately, LTx is limited by both the low number and poor quality of donated organs, and by the fact that lungs are very vulnerable to ischemia reperfusion injury (IRI), which can lead to graft dysfunction. Over the last decades, the survival and clinical outcomes of lung transplant patients have significantly improved worldwide, despite morbidity and mortality for LTx remaining high compared to other solid organ transplants.

Many advances in both basic and clinical research on LTx have emerged over the years. For instance, xenografts or bioartificial lung grafts have been studied in several animal models as an alternative approach to allogeneic LTx, but this research is still ongoing to determine its prolonged efficacy in humans. Many challenges including expanding the donor pool, inducing graft tolerance, and preventing post-transplant complications must yet be overcome to align LTx outcomes with those of other organ transplants.

Recently, ex vivo lung perfusion (EVLP) techniques have been used as a promising strategy to improve the number and the quality of lung donor grafts, with consequent reduction of post-transplant complications. The success of LTx is strongly correlated with the quality and consequent function of the lung graft and, hence, EVLP is seen as an opportunity to protect and/or repair the lungs prior to transplantation. Many researchers support the use of mesenchymal stromal/stem cells (MSCs) as a therapeutic approach to advance EVLP and, considering that these cells are believed to be capable of inducing tolerance during solid organ transplantation, MSCs can be considered a useful strategy to increase EVLP performance. Therefore, during EVLP, the administration of MSC and/or their products might pave the way for a new approach capable of increasing EVLP efficacy with the aim of improving LTx outcomes. The purpose of this chapter is to review the recent research advances in the field of LTx.

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Abbreviations

AdMSCs:

Adipose-derived MSCs

ALI:

Acute lung injury

AMSCs:

Amnion-derived MSCs

ARDS:

Acute respiratory distress syndrome

BAL:

Bronchoalveolar lavage

BM-MSCs:

Bone marrow-derived MSCs

CLAD:

Chronic lung allograft dysfunction

CM:

Conditioned medium

DCD:

Donation after circulatory death

EVLP:

Ex vivo lung perfusion

EVs:

Extracellular vesicles

EXOs:

Exosomes

IRI:

Ischemia reperfusion injury

LTx:

Lung transplantation

MSCs:

Mesenchymal stromal/stem cells

PGD:

Primary graft dysfunction

ROS:

Reactive oxygen species

UC-MSCs:

Umbilical cord-derived MSCs

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Miceli, V., Bertani, A., Pagano, V., Centi, C., Conaldi, P.G. (2023). Building Basic and Clinical Research Around Lung Transplantation. In: Bertani, A., Vitulo, P., Grossi, P.A. (eds) Contemporary Lung Transplantation. Organ and Tissue Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-20788-9_48-1

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