Normothermic machine perfusion of porcine kidneys with mesenchymal stromal cells: localisation and dose-dependency

Pool, M.B.F. (Merel) (2016) Normothermic machine perfusion of porcine kidneys with mesenchymal stromal cells: localisation and dose-dependency. thesis, Medicine.

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Abstract

Objectives: Donor kidneys of inferior quality are increasingly being accepted to decrease waiting time for a kidney transplant. Normothermic machine perfusion (NMP) of an isolated donor kidney could enable active organ conditioning and gives the opportunity for an intervention prior to transplantation. There is increasing evidence that mesenchymal stromal cells (MSCs) could have a positive effect on ischaemia-reperfusion injury. Main objective of this study was to determine if and in which quantity MSCs reach the kidney and to which structures they home when added during NMP. Methods: Porcine kidneys and autologous whole blood were obtained from two slaughterhouses in the vicinity of Groningen. Time between cardiac arrest and cold flush of kidneys was standardised at 30 min. Kidneys were cold stored for 3.5-5 hrs. Next, kidneys were perfused during 6 hours in a recirculating circuit with 350 ml washed autologous red blood cells and 500 ml Williams’ Medium E at 37°C. After 1 hour of perfusion either 0, 105, 106 or 107 cultured human adipose tissue derived MSCs were added (n=3 per group). Vital parameters were monitored and perfusate and urine samples were taken regularly. Biopsies were taken to assess renal histology and to locate and quantify the MSCs using immunohistochemistry and FACS analysis. Results: A stable NMP system and culturing routine for human MSCs was established. There was no difference in renal function during NMP between groups. MSCs were detected in the lumen of the capillaires in the glomeruli in biopsies in the 107 MSC group but not in the other groups. Quantifying the number of vital MSCs with a FACS analysis did not succeed. Conclusion: MSCs treatment did not significantly change very early renal function during NMP. After 6h of NMP, MSCs home to the lumen of the capillaires in the glomeruli. Further research is required to determine dose-dependency of the addition of MSCs.

Item Type:	Thesis (Thesis)
Supervisor name:	Faculty supervisor: and Leuvenink, prof. dr. H.G.D. and Daily supervisor: and Moers, dr. C.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 11:00
Last Modified:	25 Jun 2020 11:00
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/2042

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