Abstract

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.

Highlights

  • 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]

  • The ex vivo lung perfusion (EVLP) technique has the potential to increase the number of usable lungs up to 30% [58,60], it is not routinely used in clinical practice for lungs accepted for standard donation; rather, it is considered a tool to allow for further evaluation of lungs that are deemed to be of low quality

  • Many preclinical studies in animal models have clearly shown that the therapeutic effects of mesenchymal stromal/stem cells (MSCs) on lung injury, and on ischemia-reperfusion injury after LTx, are mediated by the reduction in inflammation [26–29,34–37,39,40,65,125,129,137,140]

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Summary

Introduction

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]. 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 [2–6] Other factors, such as postoperative graft dysfunction (PGD), infections, and rejection may contribute to post-transplant mortality [7,8]. A reduction in these adverse effects could significantly improve the success of LTx. Recently, it has been shown that the use of normothermic ex vivo lung perfusion (EVLP) may be helpful in increasing the number and improving the results of lung transplantation [13,14]. It has been shown that the use of normothermic ex vivo lung perfusion (EVLP) may be helpful in increasing the number and improving the results of lung transplantation [13,14] This procedure provides the opportunity to evaluate donor lung function, and different treatments can be used to further reduce IRI [15–17]. We describe the therapeutic properties of MSCs and their products as promising tools to improve EVLP techniques, with the ultimate goal of advancing LTx outcomes

Current Challenges in Lung Transplantation
Donor Shortage and Expansion of Donor Pool
Lung Preservation by Ex Vivo Lung Perfusion (EVLP)
Biological Role of MSCs
Therapeutic Properties of MSCs
Coli-induced mouse lung Injury
Therapeutic Effects of MSCs on Ischemia-Reperfusion Injury (IRI)
MSCs as Therapeutic Tool to Improve EVLP
Findings
Conclusions and Perspectives
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