Lung transplantation, ex-vivo reconditioning and regeneration: state of the art and perspectives

Abstract

Lung transplantation is the only therapeutic option for end-stage pulmonary failure. Nevertheless, the shortage of donor pool available for transplantation does not allow to satisfy the requests, thus the mortality on the waiting list remains high. One of the tools to overcome the donor pool shortage is the use of lung perfusion (EVLP) to preserve, evaluate and recondition selected lung grafts not otherwise suitable for transplantation. EVLP is nowadays a clinical reality and have several destinations of use. After a narrative review of the literature and looking at our experience we can assume that one of the chances to improve the outcome of lung transplantation and to overcome the donor pool shortage could be the tissue regeneration of the graft during EVLP and the immunomodulation of the recipient. Both these strategies are performed using mesenchymal stem cells (MSC). The results of the models of lung perfusion with MSC-based cell therapy open the way to a new innovative approach that further increases the potential for using of the lung perfusion platform.

NG2 as an Identity and Quality Marker of Mesenchymal Stem Cell Extracellular Vesicles

“…The former of endosomal origin, with a size roughly ranging from 40 to 150 nm [5], the latter budding from the plasma membrane, with a broader size range of 100-1000 nm [6]. In particular, EV from both adult [7] and perinatal MSC [8] have drawn attention for their immunomodulatory functions and regenerative capacity [9][10][11][12][13]. Based on these features, MSC EV are currently under investigation in many pathological contexts.…”

Ischemia–Reperfusion Injury in Lung Transplantation

“…Recently, plasmin administration during EVLP has been shown to dissolve thrombi in the lungs, resulting in reconditioning of the lungs by alleviating pulmonary IRI [110,111]. The success of fibrinolytic treatment seems crucial in DCD donors when timely heparin use might not be possible [112]. The use of fibrinolytic treatment has become a clinical standard in some EVLP centers.…”

New Trends in Regenerative Medicine: Reprogramming and Reconditioning

“…In the past, this term was used exclusively in relation to sport medicine, space flights, and, more recently, in epigenetic reconditioning of tumor cells and in transplantation medicine to improve functions of suboptimal grafts of lung, kidney, and liver. 22,23 Occasionally, a specific damaged portion of the cell or a mutant gene/protein can be identified as a hierarchical epicenter of pathogenic pathways that has profound and far-reaching consequences, akin to the opening of Pandora's box. Cell reconditioning can be achieved by activation of sirtuins or endothelial nitric oxide synthase, both advocated as powerful rejuvenation strategies.…”