Mesenchymal Stem Cells (MSC) for the amelioration of ischaemia-reperfusion injury (IRI) after deceased donor renal transplantation, a phase 1 pilot study

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In performing a renal transplant, the time spent by the graft outside the body and cooled on ice (non-perfused) is critical to its future functional capacity. With deceased donor transplants, this may be many hours and there is damage caused to the cells of the kidney by the lack of oxygenated bood suppy, which is called ischaemia. On connection of the donor renal atery to the intended recipients leg artery, blood flow is suddenly restored and the kidney is rewarmed or reperfused. Reperfusion itself is associated with further damage caused by the complex changes on blood vessels and immunological response following the period of ischaemia; the ischaemia-reperfusion injury (IRI). This may lead to delayed function of the kidney, during which the kidney undegoes repair. Changes associated with its recovery may include those that cause injury and scarring and lead to significantly worse renal function in the longer term, causing premature graft senescence and loss. There are currently few effective strategies to reduce this damaging response other than minimsation of cold ischaemia time. Many animal studies have shown that the infusion of mesenchymal stromal cells (MSC) to the recipient lessens the injury associated with IRI and allows earlier short term and better long term kidney function. We propose to use third party normal (non-immunogenic) MSC at the time of and 7 days following reperfusion of a cold stored kidney, in order to lessen this damage in a pilot study of 10 patients.

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