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Novel delivery of cellular therapy to reduce ischaemia reperfusion injury in kidney transplantation

Lookup NU author(s): Dr Emily Thompson, Lucy Bates, Dr Ibrahim Ibrahim, Dr Avinash Sewpaul, Rodrigo Figueiredo, Dr Georgie Wilkins, Dr Sam Tingle, Dr Bill Scott, Professor Andrew Mellor, Professor Andrew Fisher, Professor Simi Ali, Professor Neil Sheerin, Colin Wilson

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This is the final published version of an article that has been published in its final definitive form by Wiley-Blackwell Publishing, Inc., 2021.

For re-use rights please refer to the publisher's terms and conditions.


Abstract

Ex-vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimise organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC®) possess potent immunomodulatory properties which could minimise ischaemia reperfusion injury. We investigated the potential capability of MAPC cells in kidney NMP. Pairs (5) of human kidneys, from the same donor, were simultaneously perfused for 7-hours. Kidneys were randomly allocated to receive MAPC treatment or control. Serial samples of perfusate, urine and tissue biopsies were taken for comparison. MAPC-treated kidneys demonstrated improved urine-output (p<0.01), decreased expression of injury biomarker NGAL (p<0.01), improved microvascular perfusion on contrast enhanced ultrasound (cortex p<0.05, medulla p<0.01), downregulation of IL-1β (p<0.05) and upregulation of IL-10 (p<0.05) and Indolamine-2, 3-dioxygenase (p<0.05). A chemotaxis model demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (p<0.01). Immunofluorescence revealed pre-labelled MAPC cells in the perivascular space of kidneys during NMP. We report the first successful delivery of cellular therapy to a human kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to transplantation.


Publication metadata

Author(s): Thompson ER, Bates L, Ibrahim IK, Sewpaul A, Stenberg B, McNeill A, Figueiredo R, Girdlestone T, Wilkins GC, Tingle SJ, Scott WE, Lamos H, Mellor AL, Roobrouck VD, Ting AE, Hosgood SA, Nicholson ML, Fisher AJ, Ali S, Sheerin NS, Wilson CH

Publication type: Article

Publication status: Published

Journal: American Journal of Transplantation

Year: 2021

Volume: 21

Issue: 4

Pages: 1402-1414

Print publication date: 01/04/2021

Online publication date: 07/06/2020

Acceptance date: 21/05/2020

Date deposited: 24/05/2020

ISSN (print): 1600-6135

ISSN (electronic): 1600-6143

Publisher: Wiley-Blackwell Publishing, Inc.

URL: https://doi.org/10.1111/ajt.16100

DOI: 10.1111/ajt.16100


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