Stine Lohmann1,2, Marco Eijken2,3, Ulla Møldrup4, Bjarne K Møller1,3, James Hunter5, Cyril Moers6, Henri Leuvenink6, Rutger J Ploeg5, Marian C Clahsen-van Groningen7, Martin Hoogduijn8, Carla C Baan8, Anna Krarup Keller1,2,4, Bente Jespersen1,2. 1. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 2. Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark. 3. Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark. 4. Department of Urology, Aarhus University Hospital, Aarhus, Denmark. 5. Nuffield Department of Surgical Sciences, Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom. 6. Department of Surgery-Organ Donation and Transplantation, University of Medical Center Groningen, Groningen, the Netherlands. 7. Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. 8. Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Abstract
BACKGROUND: Mesenchymal stromal cell (MSC) therapy may improve renal function after ischemia-reperfusion injury in transplantation. Ex vivo renal intraarterial administration is a targeted delivery method, avoiding the lung vasculature, a known barrier for cellular therapies. In a randomized and blinded study, we tested the feasibility and effectiveness of MSC therapy in a donation after circulatory death autotransplantation model to improve posttransplant kidney function, using an ex vivo MSC delivery method similar to the clinical standard procedure of pretransplant cold graft flush. METHODS: Kidneys exposed to 75 minutes of warm ischemia and 16 hours of static cold storage were intraarterially infused ex vivo with 10 million male porcine MSCs (Tx-MSC, n = 8) or vehicle (Tx-control, n = 8). Afterwards, the kidneys were autotransplanted after contralateral nephrectomy. Biopsies an hour after reperfusion confirmed the presence of MSCs in the renal cortex. Animals were observed for 14 days. RESULTS: Postoperatively, peak plasma creatinine was 1230 and 1274 µmol/L (Tx-controls versus Tx-MSC, P = 0.69). During follow-up, no significant differences over time were detected between groups regarding plasma creatinine, plasma neutrophil gelatinase-associated lipocalin, or urine neutrophil gelatinase-associated lipocalin/creatinine ratio. At day 14, measured glomerular filtration rates were 40 and 44 mL/min, P = 0.66. Renal collagen content and fibrosis-related mRNA expression were increased in both groups but without significant differences between the groups. CONCLUSIONS: We demonstrated intraarterial MSC infusion to transplant kidneys as a safe and effective method to deliver MSCs to the graft. However, we could not detect any positive effects of this cell treatment within 14 days of observation.
BACKGROUND: Mesenchymal stromal cell (MSC) therapy may improve renal function after ischemia-reperfusion injury in transplantation. Ex vivo renal intraarterial administration is a targeted delivery method, avoiding the lung vasculature, a known barrier for cellular therapies. In a randomized and blinded study, we tested the feasibility and effectiveness of MSC therapy in a donation after circulatory death autotransplantation model to improve posttransplant kidney function, using an ex vivo MSC delivery method similar to the clinical standard procedure of pretransplant cold graft flush. METHODS: Kidneys exposed to 75 minutes of warm ischemia and 16 hours of static cold storage were intraarterially infused ex vivo with 10 million male porcine MSCs (Tx-MSC, n = 8) or vehicle (Tx-control, n = 8). Afterwards, the kidneys were autotransplanted after contralateral nephrectomy. Biopsies an hour after reperfusion confirmed the presence of MSCs in the renal cortex. Animals were observed for 14 days. RESULTS:Postoperatively, peak plasma creatinine was 1230 and 1274 µmol/L (Tx-controls versus Tx-MSC, P = 0.69). During follow-up, no significant differences over time were detected between groups regarding plasma creatinine, plasma neutrophil gelatinase-associated lipocalin, or urine neutrophil gelatinase-associated lipocalin/creatinine ratio. At day 14, measured glomerular filtration rates were 40 and 44 mL/min, P = 0.66. Renal collagen content and fibrosis-related mRNA expression were increased in both groups but without significant differences between the groups. CONCLUSIONS: We demonstrated intraarterial MSC infusion to transplant kidneys as a safe and effective method to deliver MSCs to the graft. However, we could not detect any positive effects of this cell treatment within 14 days of observation.
Authors: James P Hunter; Letizia Lo Faro; Kaithlyn Rozenberg; Fungai Dengu; Anne Ogbemudia; Annemarie Weissenbacher; John F Mulvey; Laura Knijff; Kishore Gopalakrishnan; Rutger J Ploeg Journal: Transpl Int Date: 2022-05-31 Impact factor: 3.842
Authors: Stina Lignell; Stine Lohmann; Kaithlyn M Rozenberg; Henri G D Leuvenink; Merel B F Pool; Kate R Lewis; Cyril Moers; James P Hunter; Rutger J Ploeg; Marco Eijken; Ulla Møldrup; Søren Krag; Carla C Baan; Bjarne Kuno Møller; Anna Krarup Keller; Bente Jespersen Journal: Transplant Direct Date: 2021-01-15
Authors: Astgik Petrosyan; Filippo Montali; Andrea Peloso; Antonio Citro; Lori N Byers; Catherine La Pointe; Mara Suleiman; Alice Marchetti; Eoin P Mcneill; Allison L Speer; Wai Hoe Ng; Xi Ren; Benedetta Bussolati; Laura Perin; Paolo Di Nardo; Vincenzo Cardinale; Jerome Duisit; Alexandra Rose Monetti; John Richard Savino; Amish Asthana; Giuseppe Orlando Journal: Front Bioeng Biotechnol Date: 2022-09-28