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Theranostic methodology for ex vivo donor lung rehabilitation.

Theranostic methodology for ex vivo donor lung rehabilitation. Med (New York, N.Y.) Pinezich, M. R., O'Neill, J. D., Guenthart, B. A., Kim, J., Vila, O. F., Ma, S. P., Chen, Y. W., Hozain, A. E., Krishnan, A., Fawad, M., Cunningham, K. M., Wobma, H. M., Van Hassel, J., Snoeck, H. W., Bacchetta, M., Vunjak-Novakovic, G. 2025: 100644

Abstract

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.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.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.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.NIH (P41 EB027062, R01HL120046, U01HL134760), CFF (VUNJAK23XX0).

View details for DOI 10.1016/j.medj.2025.100644

View details for PubMedID 40154476