Meghan R Pinezich, John D O'Neill, Brandon A Guenthart, Jinho Kim, Olaia F Vila, Stephen P Ma, Ya-Wen Chen, Ahmed E Hozain, Aravind Krishnan, Moeed Fawad, Katherine M Cunningham, Holly M Wobma, Julie Van Hassel, Hans-Willem Snoeck, Matthew Bacchetta, Gordana Vunjak-Novakovic
{"title":"用于体外供体肺康复的血清疗法方法。","authors":"Meghan R Pinezich, John D O'Neill, Brandon A Guenthart, Jinho Kim, Olaia F Vila, Stephen P Ma, Ya-Wen Chen, Ahmed E Hozain, Aravind Krishnan, Moeed Fawad, Katherine M Cunningham, Holly M Wobma, Julie Van Hassel, Hans-Willem Snoeck, Matthew Bacchetta, Gordana Vunjak-Novakovic","doi":"10.1016/j.medj.2025.100644","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Funding: </strong>NIH (P41 EB027062, R01HL120046, U01HL134760), CFF (VUNJAK23XX0).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100644"},"PeriodicalIF":12.8000,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Theranostic methodology for ex vivo donor lung rehabilitation.\",\"authors\":\"Meghan R Pinezich, John D O'Neill, Brandon A Guenthart, Jinho Kim, Olaia F Vila, Stephen P Ma, Ya-Wen Chen, Ahmed E Hozain, Aravind Krishnan, Moeed Fawad, Katherine M Cunningham, Holly M Wobma, Julie Van Hassel, Hans-Willem Snoeck, Matthew Bacchetta, Gordana Vunjak-Novakovic\",\"doi\":\"10.1016/j.medj.2025.100644\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Funding: </strong>NIH (P41 EB027062, R01HL120046, U01HL134760), CFF (VUNJAK23XX0).</p>\",\"PeriodicalId\":29964,\"journal\":{\"name\":\"Med\",\"volume\":\" \",\"pages\":\"100644\"},\"PeriodicalIF\":12.8000,\"publicationDate\":\"2025-03-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Med\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.medj.2025.100644\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Med","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.medj.2025.100644","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Theranostic methodology for ex vivo donor lung rehabilitation.
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.
期刊介绍：
Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically.
Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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