Ex Vivo Lung Perfusion Model to Study Pulmonary Tissue Extracellular Microvesicle Profiles

Vallabhajosyula, Prashanth; Korutla, Laxminarayana; Habertheuer, Andreas; Reddy, Sanjana; Schaufler, Christian; Lasky, J.; Diamond, Joshua M.; Cantu, Edward

doi:10.1016/j.athoracsur.2016.11.074

Cited by 11 publications

(15 citation statements)

References 32 publications

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“…In this respect, exosomes and extracellular vesicles (EVs) are attracting great interest. As reported by Vallabhajosyula et al [53] in a study on the perfusate from EVLP lungs, understanding EVs biology may have important diagnostic and therapeutic implications in pulmonary medicine, expanding even more the potentiality of the EVLP model.…”

Section: Discussionmentioning

confidence: 96%

Proteome Investigation of Rat Lungs Subjected to Ex Vivo Perfusion (EVLP)

et al. 2018

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Ex vivo lung perfusion (EVLP) is an emerging procedure that allows organ preservation, assessment and reconditioning, increasing the number of marginal donor lungs for transplantation. However, physiological and airflow measurements are unable to unveil the molecular mechanisms responsible of EVLP beneficial effects on lung graft and monitor the proper course of the treatment. Thus, it is urgent to find specific biomarkers that possess these requirements but also accurate and reliable techniques that identify them. The purpose of this study is to give an overview on the potentiality of shotgun proteomic platforms in characterizing the status and the evolution of metabolic pathways during EVLP in order to find new potential EVLP-related biomarkers. A nanoLC-MS/MS system was applied to the proteome analysis of lung tissues from an optimized rat model in three experimental groups: native, pre- and post-EVLP. Technical and biological repeatability were evaluated and, together with clustering analysis, underlined the good quality of data produced. In-house software and bioinformatics tools allowed the label-free extraction of differentially expressed proteins among the three examined conditions and the network visualization of the pathways mainly involved. These promising findings encourage further proteomic investigations of the molecular mechanisms behind EVLP procedure.

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Section: Discussionmentioning

confidence: 96%

Proteome Investigation of Rat Lungs Subjected to Ex Vivo Perfusion (EVLP)

et al. 2018

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“…Exosomes contain specific proteomic and RNA signatures that reflect the conditional and functional status of their cells of origin (23,28). Recently, we demonstrated that circulating transplant tissue-specific exosome characterization enables noninvasive surveillance of the transplanted solid organ in a time-sensitive, condition-specific manner (25)(26)(27). Thus, we hypothesized that transplanted stem/progenitor cells would release an exosome signal into the peripheral circulation, and characterization of stem/progenitor cell-specific exosomes would enable noninvasive surveillance of the functional activity and conditional status of the transplanted cells.…”

Section: Introductionmentioning

confidence: 99%

Circulating exosomes derived from transplanted progenitor cells aid the functional recovery of ischemic myocardium

et al. 2019

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The stem cell field is hindered by its inability to noninvasively monitor transplanted cells within the target organ in a repeatable, time-sensitive, and condition-specific manner. We hypothesized that quantifying and characterizing transplanted cell–derived exosomes in the recipient plasma would enable reliable, noninvasive surveillance of the conditional activity of the transplanted cells. To test this hypothesis, we used a human-into-rat xenogeneic myocardial infarction model comparing two well-studied progenitor cell types: cardiosphere-derived cells (CDCs) and c-kit+ cardiac progenitor cells (CPCs), both derived from the right atrial appendage of adults undergoing cardiopulmonary bypass. CPCs outperformed the CDCs in cell-based and in vivo regenerative assays. To noninvasively monitor the activity of transplanted CDCs or CPCs in vivo, we purified progenitor cell–specific exosomes from recipient total plasma exosomes. Seven days after transplantation, the concentration of plasma CPC-specific exosomes increased about twofold compared to CDC-specific exosomes. Computational pathway analysis failed to link CPC or CDC cellular messenger RNA (mRNA) with observed myocardial recovery, although recovery was linked to the microRNA (miRNA) cargo of CPC exosomes purified from recipient plasma. We further identified mechanistic pathways governing specific outcomes related to myocardial recovery associated with transplanted CPCs. Collectively, these findings demonstrate the potential of circulating progenitor cell–specific exosomes as a liquid biopsy that provides a noninvasive window into the conditional state of the transplanted cells. These data implicate the surveillance potential of cell-specific exosomes for allogeneic cell therapies.

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“…Mesenchymal stem cells may be an attractive therapeutic strategy owing to their paracrine, immunomodulating, and tissue remodeling properties [115]. Mesenchymal stem cell-derived extracellular vesicles also reportedly have the potential to attenuate lung inflammation in lung IRI [116][117][118][119]. In addition, multilineage-differentiating stress-enduring cells, which are stress-tolerant and nontumorigenic endogenous pluripotent-like stem cells, have been shown to have potential in alleviating pulmonary IRI [120].…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Ischemia–Reperfusion Injury in Lung Transplantation

Chen‐Yoshikawa

2021

Cells

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Lung transplantation has been established worldwide as the last treatment for end-stage respiratory failure. However, ischemia–reperfusion injury (IRI) inevitably occurs after lung transplantation. The most severe form of IRI leads to primary graft failure, which is an important cause of morbidity and mortality after lung transplantation. IRI may also induce rejection, which is the main cause of mortality in recipients. Despite advances in donor management and graft preservation, most donor grafts are still unsuitable for transplantation. Although the pulmonary endothelium is the primary target site of IRI, the pathophysiology of lung IRI remains incompletely understood. It is essential to understand the mechanism of pulmonary IRI to improve the outcomes of lung transplantation. Therefore, we reviewed the state-of-the-art in the management of pulmonary IRI after lung transplantation. Recently, the ex vivo lung perfusion (EVLP) system has been clinically introduced worldwide. Various promising therapeutic strategies for the protection of the endothelium against IRI, including EVLP, inhalation therapy with therapeutic gases and substances, fibrinolytic treatment, and mesenchymal stromal cell therapy, are awaiting clinical application. We herein review the latest advances in the field of pulmonary IRI in lung transplantation.

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Ex Vivo Lung Perfusion Model to Study Pulmonary Tissue Extracellular Microvesicle Profiles

Cited by 11 publications

References 32 publications

Proteome Investigation of Rat Lungs Subjected to Ex Vivo Perfusion (EVLP)

Proteome Investigation of Rat Lungs Subjected to Ex Vivo Perfusion (EVLP)

Circulating exosomes derived from transplanted progenitor cells aid the functional recovery of ischemic myocardium

Ischemia–Reperfusion Injury in Lung Transplantation

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