The Effect of Ex Vivo Preservation and Regulatory T Cells on the Development of Transplant Arteriosclerosis in a Humanized Mouse Model

Objectives: Lung transplantation is the last remaining option for treatment of end-stage lung disease. Explanted lungs can be preserved using ex vivo lung perfusion (EVLP) with the organ care system (OCS) with the idea to reduce tissue damage compared with cold storage (standard of care SOC). We compared the effect of OCS versus SOC preservation on donor arteries and the impact of recipient regulatory T-cells (Tregs) on the development of transplant arteriosclerosis (TA) in our humanized mouse model.

Methods: Segments of human pericardiophrenic arteries were procured from surplus donor lung tissue, preserved either with OCS or SOC, and implanted into the abdominal aorta of immunodeficient NRG mice. Mice were reconstituted with recipient peripheral blood mononuclear cells (PBMC), CD4 + CD25 low Treg-depleted, or Treg-enriched PBMC or left w/o PBMC. The development of TA was assessed after 28 days and systemic cytokine levels were determined.

Result: Luminal occlusion of aortic vessels without reconstitution was significantly higher in SOC compared with OCS-preserved vessels. Addition of CD4 + CD25 high Treg cells in both SOC and OCS groups had a suppressive effect on luminal occlusion compared with recipient PBMC. While systemic cytokine levels were similar, plasma sICAM-1 was significantly higher in mice with SOC-preserved vessels compared with OCS, independently from recipient PBMC.

Conclusion: We conclude that ex vivo lung preservation using the portable OCS reduces endothelial injury which may be related to the reported improved outcome (Warnecke 2018). The inflammatory response can be further suppressed by CD4 + CD25 high Treg cells in either SOC or OCS groups indicating a potential additive effect of EVLP and Treg in lung transplantation.

Publication History

Article published online:
19 February 2021