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Lookup NU author(s): Dr Emily ThompsonORCiD, Lucy BatesORCiD, Dr Ibrahim Ibrahim, Dr Avinash Sewpaul, Rodrigo Figueiredo, Dr Georgie WilkinsORCiD, Dr Sam Tingle, Dr Bill ScottORCiD, Emeritus Professor Andrew MellorORCiD, Professor Andrew FisherORCiD, Professor Simi Ali, Professor Neil SheerinORCiD, Professor Colin Wilson
This is the of an article that has been published in its final definitive form by Wiley-Blackwell Publishing, Inc., 2021.
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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.
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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