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

A. Knoefel, T. Siemeni, F. Ius, W. Sommer, J. Salman, I. Tudorache, A. Haverich, C. Falk, G. Warnecke

MHH, Hannover, Germany

Meeting: 2020 American Transplant Congress

Abstract number: A-370

Keywords: T cells

Session Information

Session Name: Poster Session A: Ischemia Reperfusion & Organ Rehabilitation

Session Type: Poster Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:00pm

 Presentation Time: 3:30pm-4:00pm

Location: Virtual

*Purpose: 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 to cold storage (standard of care SOC). We compared the effect OCS vs. SOC preservation on donor arteries and the impact of recipient regulatory T cells (Tregs) on development of transplant arteriosclerosis (TA) in our humanized mouse model.

*Methods: Segments of human pericardiophrenic arteries were procured from surplus donor lung tissue, either preserved with OCS or SOC, and implanted into the abdominal aorta of immunodeficient NRG mice. Mice were either reconstituted with recipient peripheral blood mononuclear cells (PBMC), CD4+CD25low 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.

*Results: Luminal occlusion of aortic vessels without reconstitution was significantly higher in SOC compared to OCS preserved vessels. Addition of CD4+CD25high Treg cells in both SOC and OCS groups had a suppressive effect on luminal occlusion compared to recipient PBMC. While systemic cytokine levels were similar, plasma sICAM-1 was significantly higher in mice with SOC-preserved vessels compared to OCS, independently from recipient PBMC.

*Conclusions: 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+CD25high Treg cells in either SOC or OCS groups indicating a potential additive effect of EVLP and Treg in lung transplantation.

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To cite this abstract in AMA style:

Knoefel A, Siemeni T, Ius F, Sommer W, Salman J, Tudorache I, Haverich A, Falk C, Warnecke G. The Effect of Ex Vivo Preservation and Regulatory T Cells on the Development of Transplant Arteriosclerosis in a Humanized Mouse Model [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/the-effect-of-ex-vivo-preservation-and-regulatory-t-cells-on-the-development-of-transplant-arteriosclerosis-in-a-humanized-mouse-model/. Accessed May 8, 2025.

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