Lung Transplantation, Pulmonary Endothelial Inflammation, and Ex-Situ Lung Perfusion: A Review

Forgie, Keir A.; Fialka, Nicholas M.; Freed, Darren H.; Nagendran, Jayan

doi:10.3390/cells10061417

Cited by 10 publications

(5 citation statements)

References 163 publications

(252 reference statements)

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“…In patients with persistent PGD grade 3 refractory to the aforementioned treatments, and where mechanical ventilation does not achieve adequate gas exchange, postoperative extracorporeal membrane oxygenation (ECMO) is recommended. A more in-depth analysis on treatment and prevention of PGD goes beyond the scope of this focus review and was summarized elsewhere [ 3 , 6 , 34 , 36 , 37 ].…”

Section: Pgd At Clinical Levelmentioning

confidence: 99%

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A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome

Slambrouck

Raemdonck

Vos

et al. 2022

Cells

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Primary graft dysfunction (PGD) is the clinical syndrome of acute lung injury after lung transplantation (LTx). However, PGD is an umbrella term that encompasses the ongoing pathophysiological and -biological mechanisms occurring in the lung grafts. Therefore, we aim to provide a focused review on the clinical, physiological, radiological, histological and cellular level of PGD. PGD is graded based on hypoxemia and chest X-ray (CXR) infiltrates. High-grade PGD is associated with inferior outcome after LTx. Lung edema is the main characteristic of PGD and alters pulmonary compliance, gas exchange and circulation. A conventional CXR provides a rough estimate of lung edema, while a chest computed tomography (CT) results in a more in-depth analysis. Macroscopically, interstitial and alveolar edema can be distinguished below the visceral lung surface. On the histological level, PGD correlates to a pattern of diffuse alveolar damage (DAD). At the cellular level, ischemia-reperfusion injury (IRI) is the main trigger for the disruption of the endothelial-epithelial alveolar barrier and inflammatory cascade. The multilevel approach integrating all PGD-related aspects results in a better understanding of acute lung failure after LTx, providing novel insights for future therapies.

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Section: Pgd At Clinical Levelmentioning

confidence: 99%

“…PGD grading, donor and recipient related clinical risk factors and outcome have been reviewed extensively [ 1 , 3 , 4 , 5 , 6 ]. Cellular pathways with current and future therapeutic options have been discussed in detail [ 7 , 8 , 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome

Slambrouck

Raemdonck

Vos

et al. 2022

Cells

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“…Lung transplantation (LTx) has become the treatment of choice for patients with end-stage respiratory failure and, over the past decades, the worldwide survival of lung transplant patients has increased significantly [ 1 ]. Unfortunately, the short- and long-term outcomes of LTxs are still less favorable than other solid organ transplants, the main faults being organ shortage and the fact that more than 80% of potential organ donors are not suitable or used for transplantation [ 2 , 3 , 4 , 5 , 6 ]. Moreover, other factors, such as postoperative graft dysfunction (PGD), infections, and rejection may also contribute to post-transplant mortality [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stromal/Stem Cells and Their Products as a Therapeutic Tool to Advance Lung Transplantation

Miceli

Bertani

2022

Cells

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Lung transplantation (LTx) has become the gold standard treatment for end-stage respiratory failure. Recently, extended lung donor criteria have been applied to decrease the mortality rate of patients on the waiting list. Moreover, ex vivo lung perfusion (EVLP) has been used to improve the number/quality of previously unacceptable lungs. Despite the above-mentioned progress, the morbidity/mortality of LTx remains high compared to other solid organ transplants. Lungs are particularly susceptible to ischemia-reperfusion injury, which can lead to graft dysfunction. Therefore, the success of LTx is related to the quality/function of the graft, and EVLP represents an opportunity to protect/regenerate the lungs before transplantation. Increasing evidence supports the use of mesenchymal stromal/stem cells (MSCs) as a therapeutic strategy to improve EVLP. The therapeutic properties of MSC are partially mediated by secreted factors. Hence, the strategy of lung perfusion with MSCs and/or their products pave the way for a new innovative approach that further increases the potential for the use of EVLP. This article provides an overview of experimental, preclinical and clinical studies supporting the application of MSCs to improve EVLP, the ultimate goal being efficient organ reconditioning in order to expand the donor lung pool and to improve transplant outcomes.

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“…Lung ischemia-reperfusion injury (LIRI) can occur due to trauma, atherosclerosis, pulmonary embolism, thrombosis, and some surgical procedures, such as cardiopulmonary bypass and lung transplantation [ 1 ]. LIRI has a certain incidence rate that can lead to serious clinical concurrence [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

KGF-2 Protects against Lung Ischemia-Reperfusion Injury by Inhibiting Inflammation-Induced Damage to Endothelial Barrier Function

Xia

Jin

Dong

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Lung ischemia-reperfusion injury (LIRI), which has a mortality rate of approximately 50%, is a popular topic in critical care research. Keratinocyte growth factor-2 (KGF-2) is secreted by mesenchymal cells, and it is effective in promoting the proliferation, migration, and differentiation of various epithelial cells. To date, however, only a few reports on KGF-2-related regulators in LIRI have been published. In the current study, an LIRI rat model is constructed, and the upregulation of the fibroblast growth factor receptor 2 (FGFR2) is observed in the LIRI rat model. In addition, LIRI induces NLRP1 inflammasome activation in vivo and in vitro, and KGF-2 inhibits LIRI-induced damage to pulmonary microvascular endothelial cells. Mechanistically, KGF-2 inhibits NLRP1 inflammasome and NF-κB activity. KGF-2 inhibition attenuates LIRI injury-induced damage to endothelial integrity. In conclusion, KGF-2 protects against LIRI by inhibiting inflammation-induced endothelial barrier damage.

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Lung Transplantation, Pulmonary Endothelial Inflammation, and Ex-Situ Lung Perfusion: A Review

Cited by 10 publications

References 163 publications

A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome

A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome

Mesenchymal Stromal/Stem Cells and Their Products as a Therapeutic Tool to Advance Lung Transplantation

KGF-2 Protects against Lung Ischemia-Reperfusion Injury by Inhibiting Inflammation-Induced Damage to Endothelial Barrier Function

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