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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Cell replacement in human lung bioengineering

  • Brandon A. Guenthart
    Affiliations
    Department of Surgery, Columbia University Medical Center, Columbia University, New York, New York, USA

    Department of Biomedical Engineering, Columbia University Medical Center, Columbia University, New York, New York, USA
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  • John D. O'Neill
    Affiliations
    Department of Biomedical Engineering, Columbia University Medical Center, Columbia University, New York, New York, USA
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  • Jinho Kim
    Affiliations
    Department of Biomedical Engineering, Columbia University Medical Center, Columbia University, New York, New York, USA

    Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey, USA
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  • Kenmond Fung
    Affiliations
    Department of Clinical Perfusion, Columbia University Medical Center, Columbia University, New York, New York, USA
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  • Gordana Vunjak-Novakovic
    Affiliations
    Department of Biomedical Engineering, Columbia University Medical Center, Columbia University, New York, New York, USA

    Department of Medicine, Columbia University Medical Center, Columbia University, New York, New York, USA
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  • Matthew Bacchetta
    Correspondence
    Reprint requests: Matthew Bacchetta, MD, MBA, Department of Thoracic Surgery, Vanderbilt University Medical Center, 609 Oxford House, 1313 21st Avenue South, Nashville, TN 37232. Telephone: 212-305-3408. Fax: 615-936-7003.
    Affiliations
    Department of Surgery, Columbia University Medical Center, Columbia University, New York, New York, USA
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Published:November 21, 2018DOI:https://doi.org/10.1016/j.healun.2018.11.007

      BACKGROUND

      As the number of patients with end-stage lung disease continues to rise, there is a growing need to increase the limited number of lungs available for transplantation. Unfortunately, attempts at engineering functional lung de novo have been unsuccessful, and artificial mechanical devices have limited utility as a bridge to transplant. This difficulty is largely due to the size and inherent complexity of the lung; however, recent advances in cell-based therapeutics offer a unique opportunity to enhance traditional tissue-engineering approaches with targeted site- and cell-specific strategies.

      METHODS

      Human lungs considered unsuitable for transplantation were procured and supported using novel cannulation techniques and modified ex-vivo lung perfusion. Targeted lung regions were treated using intratracheal delivery of decellularization solution. Labeled mesenchymal stem cells or airway epithelial cells were then delivered into the lung and incubated for up to 6 hours.

      RESULTS

      Tissue samples were collected at regular time intervals and detailed histologic and immunohistochemical analyses were performed to evaluate the effectiveness of native cell removal and exogenous cell replacement. Regional decellularization resulted in the removal of airway epithelium with preservation of vascular endothelium and extracellular matrix proteins. After incubation, delivered cells were retained in the lung and showed homogeneous topographic distribution and flattened cellular morphology.

      CONCLUSIONS

      Our findings suggest that targeted cell replacement in extracorporeal organs is feasible and may ultimately lead to chimeric organs suitable for transplantation or the development of in-situ interventions to treat or reverse disease, ultimately negating the need for transplantation.

      Keywords

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