Abstract: FR-PO1008
Delivery of Point-of-Care Adipose-Derived Regenerative Cell Population to Kidneys during Normothermic Machine Perfusion
Session Information
- Transplantation: Basic
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2101 Transplantation: Basic
Authors
- Pearson, Robert, Queen Elizabeth University Hospital, Glasgow, United Kingdom
- Norton, William Geoffrey, Queen Elizabeth University Hospital, Glasgow, United Kingdom
- Mark, Patrick Barry, University of Glasgow, Glasgow, United Kingdom
- Clancy, Marc J., Queen Elizabeth University Hospital, Glasgow, United Kingdom
Background
Normothermic machine perfusion (NMP) of kidneys provides a period of assessment prior to implantation with the potential benefit of improving organ utilisation. Furthermore, it provides an opportunity to deliver therapeutics without negotiating the systemic circulation. The immunoregulatory properties of adipose-derived regenerative cells (ADRC) have been shown in numerous organ systems, including the kidney, and can be readily extracted from adipose tissue without the need for culture expansion.
Methods
Eight declined human kidneys were randomised to four hours of blood-based NMP with (n=3) or without (n=5) the administration of ADRC. The ADRC population was extracted from 150ml of donor peri-renal adipose tissue using the approved Celution® 800/CRS System and delivered directly via the arterial limb of the perfusion circuit. Samples of urine, perfusate and graft biopsies were taken for subsequent analysis.
Results
ADRC harvest from peri-renal tissue had a cell viability of 78-85% with cell number of between 1.2 and 1.4 million. There were no adverse events, such as glomerular thrombus, with NMP + ADRC. There were no apparent differences between NMP + ADRC and NMP alone with regard to urine output, perfusion parameters or histological grading of acute tubular injury. RNA sequencing demonstrated 24 differentially expressed genes with NMP + ADRC. Gene ontology analysis revealed upregulated biological processes within the ADRC group including nephron tubule epithelial cell differentiation.
Conclusion
ADRC were successfully extracted from donor perirenal tissue and delivered at point-of-care without culture expansion to kidneys during NMP, with no apparent adverse haemodynamic effect nor adverse histological change. Although theoretically desirable differential gene expression was demonstrated, further studies incorporating implantation will be required to assess whether this appoach provides meaningful clinical benefit.
Heatmap of top 24 differentially expressed genes