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Advanced imaging techniques for assessing the potential of a cell therapy to improve the health of ex vivo perfused marginal kidneys

Project description

Regenerative cell therapy for kidney transplants

End-stage kidney disease is the final, life-threatening stage of chronic kidney failure, where the kidneys can no longer function on their own. For many patients, kidney transplantation is the best treatment, offering freedom from dialysis and improved quality of life. However, due to a shortage of suitable organs, older and more vulnerable ‘marginal’ kidneys are increasingly used. With the support of the Marie Skłodowska-Curie Actions programme, the PerfusedKidneys project will investigate a regenerative cell therapy using adipose-derived cells taken from fat surrounding donor kidneys. Researchers will combine ex vivo machine perfusion with magnetic particle imaging to monitor how these cells distribute within the kidney and evaluate their therapeutic effects. The goal is to restore marginal kidneys, increasing transplant success and reducing reliance on dialysis.

Objective

Kidney transplantation is the gold-standard for end-stage kidney disease (ESKD) but there is a shortage of organs. To increase organ numbers, kidneys from deceased donors aged over 60 are now often used. These so-called “marginal” kidneys are susceptible to the ischemic tissue damage that occurs during transplantation, and tend not to function as well, nor last as long, as kidneys from younger donors. Cell therapies administered into the renal artery prior to transplantation have potential to repair marginal kidneys. Adipose derived regenerative cells (ADRCs) are an attractive cell therapy because they can be isolated from the perinephric fat surrounding the donor kidneys, and can improve kidney health in rodent models. However, difficulties in evaluating ADRCs in human donor kidneys is a barrier to clinical translation. We need to monitor the biodistribution of the cells within the kidneys to ensure they do not form emboli, as well as measure the therapeutic effects of the cells on kidney function and tissue health. Recent technological advances in machine perfusion and imaging makes it possible to overcome these barriers. With machine perfusion, kidneys can be perfused outside the body (ex vivo) prior to transplantation, allowing their function to be assessed. Furthermore, a highly sensitive novel imaging technique called “magnetic particle imaging” (MPI), will enable the biodistribution of labelled cells to be determined with great accuracy. In this project, I aim to address these questions using marginal human kidneys that are not deemed suitable for transplantation. The University of Liverpool is uniquely positioned to host my project, being the only centre in Europe with expertise in both ex vivo perfusion as well as having an MPI scanner. If successful, my project could expedite the clinical translation of ADRCs and improve the performance of marginal kidneys. This would improve the lives of ESKD patients by keeping them off dialysis for longer.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

THE UNIVERSITY OF LIVERPOOL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 260 347,92
Address
BROWNLOW HILL 765 FOUNDATION BUILDING
L69 7ZX LIVERPOOL
United Kingdom

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Region
North West (England) Merseyside Liverpool
Activity type
Higher or Secondary Education Establishments
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Total cost

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