A IRISH1,2, S SWAMINATHAN1, S FIDLER4,6, LD’ORSOGNA2,4,6, R SINNIAH2,5,6, M STURM3
1Fiona Stanley Hospital, Murdoch, Australia; 2University of Western Australia,Nedlands, Australia; 3Cell and Tissue Therapies Western Australia, Perth, Australi; 4Department of Immunology, Murdoch, Australia; 5Department of Histopathology,Murdoch, Australia; 6Pathwest Laboratory, Nedlands, Australia
Background: Ischaemia Reperfusion Injury (IRI) is associated with delayed graft function (DGF) and reduced graft survival. Mesenchymal Stromal cells (MSCs) have anti-inflammatory and immune regulating properties that may mitigate IRI.
Aims: A Phase 1 study to assess safety and tolerability of bone-marrow derived allogeneic MSCs in deceased donor renal transplant recipients (RTR).
Methods: We administered MSCs from 2 donors to 12 RTRs in a dose of 2 x 106 cells/kg within 2 hours of reperfusion and on day 7. Patients received standard induction and immunosuppression. Patients were followed for 12 months with monitoring of graft function, HLA antibody, infectious complications and graft biopsy at 3 and 12 months. We compared them with 98 deceased donor controls (DC) performed between 2012-15.
Results: This is the first trial of allogeneic MSCs in deceased donor renal transplant recipients. 12 patients (5 male, mean age 45) were included in the study. There were no infusion reactions. Compared with DC, the MSC recipients had a higher proportion of regrafts (33% vs 13%) and shipped kidneys but no difference in ischaemic time (10±3 vs 10±4 hours) or DGF (17% vs 18%). Compared with DC, creatinine at 1 (134 vs 182 μmol/L) and 3 (123 vs 168 μmol/L) months was not significantly different. 2/12 MSCr had BPAR; one due to recurrent non-compliance and another receiving a steroid free protocol. There were no significant infectious complications (viral or bacterial). Serial HLA monitoring detected de novo DSA against 1 kidney but no MSC donor at 12 months.
Conclusions: Immediate infusion of MSCs was well tolerated with no early safety signals of allogenicity, graft injury or over-immunosuppression. Larger controlled trials are warranted.