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

Descripción del proyecto

Terapia celular regenerativa para trasplantes de riñón

La insuficiencia renal terminal es la fase final, potencialmente mortal, de la insuficiencia renal crónica, en la que los riñones ya no pueden funcionar sin ayuda. Para muchos pacientes, el trasplante de riñón es el mejor tratamiento, ya que les libera de la diálisis y mejora su calidad de vida. Sin embargo, debido a la escasez de órganos adecuados, cada vez se utilizan más los riñones «marginales», más viejos y vulnerables. Con el apoyo de las Acciones Marie Skłodowska-Curie, el equipo del proyecto PerfusedKidneys investigará una terapia celular regenerativa con células derivadas de tejido adiposo extraídas de la grasa que rodea los riñones de donantes. Los investigadores combinarán la perfusión «ex vivo» de la máquina con imágenes de partículas magnéticas para controlar cómo se distribuyen estas células en el riñón y evaluar sus efectos terapéuticos. El objetivo es restaurar los riñones marginales, lo que aumentaría el éxito del trasplante y reduciría la dependencia de la diálisis.

Objetivo

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.