Mesenchymal stromal cell treatment during ex vivo normothermic machine perfusion of donor kidneys - a porcine autotransplantation study

M.B.F. Pool, S. Lohmann, K.M. Rozenberg, M. Eijken, R.J. Ploeg, J. Hunter, C. Moers, A. Krarup Keller, U. Moldrop, H.G.D. Leuvenink, B. Jespersen

Wednesday 4 march 2020

15:00 - 15:10h at Joep Nicolas zaal

Parallel session: Parallel sessie IV – Basale abstracts

Background: Donor kidneys of inferior quality are increasingly being accepted to decrease waiting time for a transplant. Normothermic machine perfusion (NMP) could provide superior organ preservation compared to other preservation methods. In addition, it offers the unique opportunity for active interventions to an isolated organ prior to transplantation. There is increasing evidence that mesenchymal stromal cells (MSCs) could have a positive effect on ischaemic injury. However, in most studies MSCs are administered to recipients after transplantation, which exposes the whole patient to circulating allogeneic cells. In this preclinical study, we aimed to investigate whether MSCs can also be administered ex vivo during pre-transplant NMP and whether this MSC treatment improved early graft function.

Methods: Female laboratory pigs were used in this series of auto-transplantation experiments. Four experimental groups were defined (n=7 per group) and kidneys were randomly assigned to each group. After 75 minutes of warm ischaemia kidneys were subjected to four different preservation strategies. In group 1 kidneys underwent oxygenated HMP for 14 hours (ox-HMP) and in group 2 oxygenated HMP for 14 hours was followed by NMP for 4 hours (NMP). Kidneys in group 3 were also subjected to oxygenated HMP for 14 hours and NMP for 4 hours but after 1 hour 10 million porcine adipose tissue derived MSCs were added to the circuit (NMP + pMSC). Group 4 followed the same protocol as group 3 but instead of porcine MSCs, 10 million human renal adipose tissue derived MSCs (NMP + hMSC) were added. Subsequently, all kidneys were autotransplanted and pigs were observed for 14 days. Creatinine levels were monitored and GFR measurement took place on day 14.

Results: Adding MSCs during pre-transplant renal NMP proved to be safe; no embolisms occurred and MSC treated kidneys did not show inferior posttransplant function. Posttransplant serum creatinine values in all groups were comparable, with slightly lower levels in the groups in which the kidneys were subjected to NMP in addition to HMP.

Conclusions: In this relatively short follow-up period, we did not see an effect of treatment with MSCs, but as viable MSCs remained detectable in the transplanted kidney at postoperative day 14, this allows for possible long-term effects which remain to be studied.