Immune Characterization of a Xenogeneic Cross Circulation System for Ex Vivo Human Lung Support
Rehabilitation of injured donor lungs can reduce the shortage of organs suitable for transplantation. We previously established a platform for the maintenance and recovery of extracorporeal human lungs using cross-circulation (XC) with a porcine host. Here, we characterize the human-swine immunologi...
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| Published in: | The Journal of heart and lung transplantation Vol. 41; no. 4; pp. S18 - S19 |
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| Main Authors: | , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Elsevier Inc
01-04-2022
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| Online Access: | Get full text |
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| Summary: | Rehabilitation of injured donor lungs can reduce the shortage of organs suitable for transplantation. We previously established a platform for the maintenance and recovery of extracorporeal human lungs using cross-circulation (XC) with a porcine host. Here, we characterize the human-swine immunologic interactions in this xenogeneic system.
Human donor lungs declined for clinical transplantation were placed on XC with immunosuppressed (methylprednisolone, mycophenolate, tacrolimus), complement-depleted (Cobra Venom Factor) porcine hosts. Longitudinal analyses of the extracorporeal lung and porcine host were performed over 24 hours. For one of these lung (n = 1), single-cell lung suspensions and paraffin-embedded slides were prepared from biopsies of the lung collected at pre-XC baseline, 1h, and 24h. Infiltration of swine CD45+ immune cells and deposition of swine IgG and IgM in the human lung were assessed by immunohistochemistry and flow cytometry.
The extracorporeal lung demonstrated improved PaO2/FiO2 (602%), dynamic compliance (238%), and gas exchange (O2, 974%; CO2, 198%) over the course of XC. Populations of human and porcine CD45+ leukocytes were readily identified within the post-XC lung. Human immune cells represented 1.48% and porcine immune cells represented 0.99% of isolated live single cells (Figure 1A). Infiltration of CD45+ porcine leukocytes into the lung increased over time, such that porcine neutrophils were visualized in the alveolar spaces (Figure 1B). By flow cytometry, porcine IgG was localized to lung epithelial cells (Figure 1C). Diffuse deposition of IgG and IgM was also detected by IHC (Figure 1D).
In the xenogeneic XC system, porcine immune cell and immunoglobulin infiltration of the extracorporeal human lung can be detected. Despite this, XC was sufficient to facilitate physiologic improvement in the human lung. Further work is needed to minimize cross-species immune responses during ex vivo organ support. |
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| ISSN: | 1053-2498 1557-3117 |
| DOI: | 10.1016/j.healun.2022.01.038 |