Mitigation of Primary Graft Dysfunction in Lung Transplantation: Current Understanding and Hopes for the Future

Wilkey, Barbara J.; Abrams, Benjamin

doi:10.1177/1089253219881980

Cited by 15 publications

(16 citation statements)

References 97 publications

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“…Survival rates after LTx have improved, yet outcomes are still poorer than other solid organ transplants [ 3 , 6 ]. The advances of the lung preservation techniques and the better understanding of the main mechanisms governing IRI processes can lead to a significant reduction in the incidence of lung PGD [ 118 ]. This condition is a type of acute lung injury that results from IRI and represents the major cause of early post-transplant morbidity and mortality [ 119 ].…”

Section: Mesenchymal Stromal/stem Cell (Msc)-based Therapeutic Approa...mentioning

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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Section: Mesenchymal Stromal/stem Cell (Msc)-based Therapeutic Approa...mentioning

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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“…Imaging and the ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) (P/F) are used for the grading and clinical prognostic evaluation of PGD (Table 2 ). 9 , 13 , 14 Moreover, grade 3 PGD is strongly correlated with the decline of forced expiratory volume in 1 s (FEV1) and the development of bronchiolitis obliterans syndrome (BOS). 15 Strict preoperative criteria for donor and recipient selection and refinement of lung perfusion preservation and surgical techniques can reduce the occurrence of PGD to some extent.…”

Section: Primary Graft Dysfunctionmentioning

confidence: 99%

Graft dysfunction and rejection of lung transplant, a review on diagnosis and management

Sun

Deng

Chen

et al. 2022

Clinical Respiratory J

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“…From these studies, we concluded that HLA-DSAs may induce immune responses to TaAgs, which either alone or in combination of both increases the risk of BOS. Significantly, primary graft dysfunction (PGD) is also a well-known risk factor for the development of BOS ( 40 – 42 ). Inflammation and tissue remodeling in the recipient and the surgical stress during transplantation can lead to the expression of sequestrated antigenic epitopes of TaAgs present in the lungs, and pre-existing immune responses to TaAgs can lead to PGD ( 43 ).…”

Section: Immune Responses Against Hla and Non-hla Taags And Allograft...mentioning

confidence: 99%

Extracellular Vesicles Mediate Immune Responses to Tissue-Associated Self-Antigens: Role in Solid Organ Transplantations

et al. 2022

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Transplantation is a treatment option for patients diagnosed with end-stage organ diseases; however, long-term graft survival is affected by rejection of the transplanted organ by immune and nonimmune responses. Several studies have demonstrated that both acute and chronic rejection can occur after transplantation of kidney, heart, and lungs. A strong correlation has been reported between de novo synthesis of donor-specific antibodies (HLA-DSAs) and development of both acute and chronic rejection; however, some transplant recipients with chronic rejection do not have detectable HLA-DSAs. Studies of sera from such patients demonstrate that immune responses to tissue-associated antigens (TaAgs) may also play an important role in the development of chronic rejection, either alone or in combination with HLA-DSAs. The synergistic effect between HLA-DSAs and antibodies to TaAgs is being established, but the underlying mechanism is yet to be defined. We hypothesize that HLA-DSAs damage the transplanted donor organ resulting in stress and leading to the release of extracellular vesicles, which contribute to chronic rejection. These vesicles express both donor human leukocyte antigen (HLA) and non-HLA TaAgs, which can activate antigen-presenting cells and lead to immune responses and development of antibodies to both donor HLA and non-HLA tissue-associated Ags. Extracellular vesicles (EVs) are released by cells under many circumstances due to both physiological and pathological conditions. Primarily employing clinical specimens obtained from human lung transplant recipients undergoing acute or chronic rejection, our group has demonstrated that circulating extracellular vesicles display both mismatched donor HLA molecules and lung-associated Ags (collagen-V and K-alpha 1 tubulin). This review focuses on recent studies demonstrating an important role of antibodies to tissue-associated Ags in the rejection of transplanted organs, particularly chronic rejection. We will also discuss the important role of extracellular vesicles released from transplanted organs in cross-talk between alloimmunity and autoimmunity to tissue-associated Ags after solid organ transplantation.

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Mitigation of Primary Graft Dysfunction in Lung Transplantation: Current Understanding and Hopes for the Future

Cited by 15 publications

References 97 publications

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

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

Graft dysfunction and rejection of lung transplant, a review on diagnosis and management

Extracellular Vesicles Mediate Immune Responses to Tissue-Associated Self-Antigens: Role in Solid Organ Transplantations

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