Med (New York, N.Y.) · 2025
Theranostic methodology for ex vivo donor lung rehabilitation.
СтатьяResearch Support, N.I.H., IntramuralКомментарийНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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История · было → стало
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Pinezich Meghan R, O'Neill John D, Guenthart Brandon A, Kim Jinho, Vila Olaia F, Ma Stephen P, Chen Ya-Wen, Hozain Ahmed E, Krishnan Aravind, Fawad Moeed, Cunningham Katherine M, Wobma Holly M, Van Hassel Julie, Snoeck Hans-Willem, Bacchetta Matthew, Vunjak-Novakovic Gordana
Аннотация
BACKGROUND: About 80% of donor lungs are not utilized for transplantation. Cross-circulation of ex vivo lungs with a support swine enables the rehabilitation of donor lungs that are initially deemed unsuitable for transplantation. Robust therapeutic and diagnostic modalities are needed for ex vivo lung rehabilitation; however, no standardized "theranostic" methodology has been reported.
METHODS: Ex vivo lungs (n = 23; 17 injured and 6 controls) with multi-focal contusion (n = 6, human), gastric aspiration injury (n = 8, swine), ischemia-reperfusion injury (n = 3, swine), or no injury (n = 6, swine) were used to develop a therapeutic and diagnostic (theranostic) methodology for ex vivo lung rehabilitation during cross-circulation. Airway (bronchoscopic, nebulized), intravascular, and transpleural access enabled sample collection and therapeutic delivery. Diagnostic modalities included non-invasive imaging, functional testing, and molecular assays. Therapeutic modalities included bronchoalveolar lavage, surfactant replacement, recruitment maneuvers, and cell/organoid delivery. Real-time tracking of delivered cells was performed via fluorescence and bioluminescence imaging.
FINDINGS: Diagnostic assessments revealed tissue-, cell-, and molecular-level insights at global and regional scales of ex vivo lungs during cross-circulation, which informed therapeutic management and interventions to recover donor lungs. Mesenchymal stromal cells and lung organoids were delivered bronchoscopically and transpleurally, tracked non-invasively during cross-circulation, and observed to localize within the parenchyma.
CONCLUSIONS: Application of a theranostic methodology during cross-circulation enabled real-time ex vivo lung assessment and rehabilitation across a variety of lung injuries to help increase clinical utilization of donor lungs in the future.
FUNDING: NIH (P41 EB027062, R01HL120046, U01HL134760), CFF (VUNJAK23XX0).
METHODS: Ex vivo lungs (n = 23; 17 injured and 6 controls) with multi-focal contusion (n = 6, human), gastric aspiration injury (n = 8, swine), ischemia-reperfusion injury (n = 3, swine), or no injury (n = 6, swine) were used to develop a therapeutic and diagnostic (theranostic) methodology for ex vivo lung rehabilitation during cross-circulation. Airway (bronchoscopic, nebulized), intravascular, and transpleural access enabled sample collection and therapeutic delivery. Diagnostic modalities included non-invasive imaging, functional testing, and molecular assays. Therapeutic modalities included bronchoalveolar lavage, surfactant replacement, recruitment maneuvers, and cell/organoid delivery. Real-time tracking of delivered cells was performed via fluorescence and bioluminescence imaging.
FINDINGS: Diagnostic assessments revealed tissue-, cell-, and molecular-level insights at global and regional scales of ex vivo lungs during cross-circulation, which informed therapeutic management and interventions to recover donor lungs. Mesenchymal stromal cells and lung organoids were delivered bronchoscopically and transpleurally, tracked non-invasively during cross-circulation, and observed to localize within the parenchyma.
CONCLUSIONS: Application of a theranostic methodology during cross-circulation enabled real-time ex vivo lung assessment and rehabilitation across a variety of lung injuries to help increase clinical utilization of donor lungs in the future.
FUNDING: NIH (P41 EB027062, R01HL120046, U01HL134760), CFF (VUNJAK23XX0).