The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-eighth adult lung transplantation report — 2021; Focus on recipient characteristics

Chambers, Daniel C.; Perch, Michael; Zuckermann, Andreas; Cherikh, Wida S.; Harhay, Michael O.; HayesJr., Don; Hsich, Eileen; Khush, Kiran K.; Potena, Luciano; Sadavarte, Aparna; Lindblad, Kelsi; Singh, Tajinder P.; Stehlik, Josef

doi:10.1016/j.healun.2021.07.021

Cited by 282 publications

(170 citation statements)

References 20 publications

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“…There is typically no response to general anti-inflammatory therapies such as glucocorticosteroids and immunosuppressants. Lung transplantation is currently the most effective therapy, with a 50% chance survival rate 5 years post-transplantation ( Chambers et al, 2021 ). Drugs such as pirfenidone and nintedanib have been used for patients who are ineligible for transplantation in an attempt to slow the progression of disease.…”

Section: Introductionmentioning

confidence: 99%

Effect of 2D and 3D Culture Microenvironments on Mesenchymal Stem Cell-Derived Extracellular Vesicles Potencies

Kusuma

Zhu

et al. 2022

Front. Cell Dev. Biol.

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Therapeutic benefits of mesenchymal stem cells (MSCs) are now widely believed to come from their paracrine signalling, i.e. secreted factors such as cytokines, chemokines, and extracellular vesicles (EVs). Cell-free therapy using EVs is an active and emerging field in regenerative medicine. Typical 2D cultures on tissue culture plastic is far removed from the physiological environment of MSCs. The application of 3D cell culture allows MSCs to adapt to their cellular environment which, in turn, influences their paracrine signalling activity. In this study we evaluated the impact of 3D MSCs culture on EVs secretion, cargo proteome composition, and functional assessment in immunomodulatory, anti-inflammatory and anti-fibrotic properties.MSC-EVs from 2D and 3D cultures expressed classical EV markers CD81, CD63, and CD9 with particle diameter of <100 nm. There were distinct changes in immunomodulatory potencies where 3D cultures exhibited reduced indoleamine 2,3-dioxygenase (IDO) activity and significantly reduced macrophage phagocytosis. Administration of 2D and 3D EVs following double dose bleomycin challenge in aged mice showed a marked increase of bodyweight loss in 3D group throughout days 7–28. Histopathological observations of lung tissues in 3D group showed increased collagen deposition, myofibroblast differentiation and leukocytes infiltrations. Assessment of lung mechanics showed 3D group did not improve lung function and instead exhibited increased resistance and tissue damping. Proteome profiling of MSC-EV composition revealed molecular enrichment of EV markers (compared to parental cells) and differential proteome between EVs from 2D and 3D culture condition associated with immune-based and fibrosis/extracellular matrix/membrane organization associated function.This study provides insight into distinct variation in EV protein composition dependent on the cellular microenvironment of the parental cells, which could have implications in their therapeutic effect and potency. Overall, this work suggests that EVs produced from 3D MSC cultures did not enhance typical MSC-EV properties expected from 2D cultures (immunomodulation, anti-fibrotic, anti-inflammatory). The outcome highlights critical differences between MSC-EVs obtained from different culture microenvironments, which should be considered when scaling up MSC culture for clinical manufacturing.

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Section: Introductionmentioning

confidence: 99%

Effect of 2D and 3D Culture Microenvironments on Mesenchymal Stem Cell-Derived Extracellular Vesicles Potencies

Kusuma

Zhu

et al. 2022

Front. Cell Dev. Biol.

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“…Survival after lung transplant for individuals with CF has improved over the last three decades, and highly effective modulators may reduce co-morbidities impacting survival. Five year survival conditional survival is nearly 80% for individuals with CF which is 10–15% higher compared to other diagnosis group [41 ▪ ]. The median survival for CF recipients is nearly 10 years, several years longer than for other diagnosis groups.…”

Section: Transplant Outcomes and Use Of Cystic Fibrosis Transmembrane...mentioning

confidence: 89%

Cystic fibrosis: candidate selection and impact of the cystic fibrosis transmembrane conductance regulator therapy

Lehr

Pilewski

2022

Current Opinion in Organ Transplantation

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Purpose of reviewOver the past decade, the development of highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators has dramatically ameliorated the manifestations of CF for most patients. Perhaps most importantly, CFTR modulators impact the development and progression of advanced lung disease (ALD) and are changing the CF population accessing lung transplant.Recent findingsA recent phase 3 trial of elexacaftor/tezacaftor/ivacaftor (ETI) demonstrated efficacy for individuals with at least one copy of the most common CF mutation, F508del. Studies of CFTR modulator therapy in patients with ALD have demonstrated similar improvements in lung function, nutrition, and pulmonary exacerbation frequency as seen in individuals with higher lung function. Due to improvements with ETI, rates of lung transplant for CF have declined and individuals are achieving stability in lung function. Nevertheless, the Cystic Fibrosis Foundation guidelines for lung transplant referral should be used to guide referral decisions for all individuals with CF, including those on CFTR modulator therapy, to allow remediation of modifiable barriers to transplant. ETI may be used in the posttransplant setting but for selected individuals and with close monitoring.SummaryIncreasing access to highly effective CFTR modulators has changed the trajectory of lung disease in CF for many, but not all, individuals and there remain individuals who cannot access therapy or whose mutations do not respond to modulators. Lung transplant remains an important treatment option for individuals with advanced CF lung disease. Increasing attention will be required to optimize decisions of when to list for transplant.

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“…Over the past 30 years lung transplantation has become a commonly performed therapy providing an opportunity to improve longevity and regain quality of life 1 . Improved surgical techniques and the use of oral calcineurin inhibitors have resulted in early post‐operative benefits but medium and long‐term outcomes are poor.…”

Section: Figurementioning

confidence: 99%

“…Improved surgical techniques and the use of oral calcineurin inhibitors have resulted in early post‐operative benefits but medium and long‐term outcomes are poor. Since the 1990s, BOS remains the leading cause of mortality and a current posttransplant median survival of 6.7 years has not changed substantially from prior decades 1 . With systemic cyclosporine and tacrolimus, early rejection is suppressed, but a persistent alloresponse to bronchiolar cells then frequently develops results in chronic lung allograft dysfunction (CLAD) manifesting commonly as bronchiolitis obliterans syndrome (BOS).…”

Section: Figurementioning

confidence: 99%

Capitalizing on the concept of local immune suppression by inhalation for lung transplant recipients

Iacono

2022

American Journal of Transplantation

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The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-eighth adult lung transplantation report — 2021; Focus on recipient characteristics

Cited by 282 publications

References 20 publications

Effect of 2D and 3D Culture Microenvironments on Mesenchymal Stem Cell-Derived Extracellular Vesicles Potencies

Effect of 2D and 3D Culture Microenvironments on Mesenchymal Stem Cell-Derived Extracellular Vesicles Potencies

Cystic fibrosis: candidate selection and impact of the cystic fibrosis transmembrane conductance regulator therapy

Capitalizing on the concept of local immune suppression by inhalation for lung transplant recipients

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