Use Of Perirenal Adipose Tissue As A Source Of Donor Cells Allowing Evaluation Of Endothelial Inflammation And Quality Of Expanded Criteria Kidneys

R. Boissier¹, L. Lyonnet², P. Francois³, M. Meunier⁴, B. Gondran-Tellier⁵, T. Legris⁶, J. Magalon⁵, C. Picard⁷, F. Dignat George⁵, E. Lechevallier⁸, G. Karsenty⁸, F. Sabatier⁹, P. Paul¹

¹INSERM 1263, Centre de recherche en cardiovasculaire et nutrition, INSERM, Aix Marseille Univ, Assistance Publique Hopitaux Marseille, Marseille, France, ²Vascular Biology and Hematology department, Assistance publique Hopitaux Marseille (AP-HM), Marseille, France, ³INSERM 1263, Centre de recherche en cardiovasculaire et nutrition, INSERM, Aix Marseille Univ., Marseille, France, ⁴Nephrology Dialysis and Renal Transplantation Center, AP-HM, Marseille, France, ⁵INSERM 1263, C2VN, INSERM, Aix Marseille Univ., Marseille, France, ⁶Nephrology Dialysis and Renal Transplantation Center, AP-HM, Marseille, France, ⁷Etablissement Français du Sang, Alpes Méditerranée, Marseille, France, ⁸Urology and Transplantation Unit , AP-HM, Marseille, France, ⁹INSERM 1263, Centre de recherche en cardiovasculaire et nutrition, INSERM, Aix Marseille Univ, Marseille, France

Meeting: 2019 American Transplant Congress

Abstract number: A144

Keywords: Age factors, Alloantibodies, Donors, marginal, Endothelial cells

Session Information

Session Name: Poster Session A: Biomarkers, Immune Monitoring and Outcomes

Session Type: Poster Session

Date: Saturday, June 1, 2019

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Hall C & D

*Purpose: Use of expanded-criteria donor (ECD) kidneys is a perspective to overcome organ shortage. Age and donor-related co-morbidy factors are known to affect graft function after kidney transplantation. Our working hypothesis was that the perirenal adipose tissue (PR-AT) could be a relevant source of donor-derived cells allowing assessment of donor endothelial cell dysfunction and organ quality in ECD donors

*Methods: Perirenal (PR) adipose tissue was obtained from 40 kidney donors (10 living and 30 deceased donors with various comorbidities factors). Collagenase digestion allowed isolation of the Stromal Vascular Fraction (SVF). RNAseq transcriptomic analysis was performed on PR-SVF from 5 ECD and 5 non-ECD donors. The SVF-dependent formation of capillary-like structures was evaluated in an in vitro Matrigel^TM assay. The distribution of CD45+ and CD45- cell subsets within PR-SVF was analyzed by flow cytometry. CD144+ endothelial cells were purified from PR-SVF and tested for their capacity to bind transplant recipient circulating alloantibodies and induce FcR-driven antibody dependent NK cell cytotoxicity.

*Results: The distribution of the leucocyte, endothelial, stromal, and pericyte cell subsets were comparable in ECD-SVF and non-ECD -SVF. SVF from ECD donors displayed a differential molecular signature characterized by over-expression of inflammatory markers (CXCL1, FGF1..). Gene Set and Cell type analyses show an enrichment of terms related to immune activation and an increase in NKT, CLP cells and cytokine activity in ECD-SVF. CD144+ endothelial cells purified from PR-SVF were potent targets allowing indexing alloantibody cytotoxic potential resulting from FcR-driven antibody dependent NK cell cytotoxicity.

*Conclusions: In conclusion, we validated the feasibility of obtaining donor derived endothelial cells from the perirenal adipose tissue and provide evidence that such cells can be used in the individualized assay of donor-related inflammatory parameters that may further associate to kidney allograft dysfunction and immune driven vasculopathy.

To cite this abstract in AMA style:

Boissier R, Lyonnet L, Francois P, Meunier M, Gondran-Tellier B, Legris T, Magalon J, Picard C, George FDignat, Lechevallier E, Karsenty G, Sabatier F, Paul P. Use Of Perirenal Adipose Tissue As A Source Of Donor Cells Allowing Evaluation Of Endothelial Inflammation And Quality Of Expanded Criteria Kidneys [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/use-of-perirenal-adipose-tissue-as-a-source-of-donor-cells-allowing-evaluation-of-endothelial-inflammation-and-quality-of-expanded-criteria-kidneys/. Accessed November 22, 2024.

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