Intra-renal arterial injection of autologous bone marrow mesenchymal stromal cells ameliorates cisplatin-induced acute kidney injury in a rhesus Macaque mulatta monkey model |
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| Affiliation: | 1. Department of Biology, Kharazmi University, Tehran, Iran;2. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;3. Department of Regenerative Medicine at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;4. Urology and Nephrology Research Center, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran;5. Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran;6. Department of Veterinary Radiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran;7. Department of Clinical Sciences, Faculty of Veterinary Medicine, Karaj Branch, Islamic Azad University, Karaj, Iran;8. Department of Andrology at the Reproductive Biomedicine Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;9. Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, Iran;10. Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran;11. Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran;1. Department of Pediatric Hematology/Oncology, IRCCS Bambino Gesù Children''s Hospital, Rome, Italy;2. University of Pavia, Pavia, Italy;3. Department of Biomedical, Surgical, Dental Sciences, University of Milan, Italy;4. UCV Neurobiology, IRCCS Neurological Institute, Carlo Besta, Milan, Italy;1. Professor, Department of Oral-Craniofacial and Plastic Facial Surgery, Goethe University, Hospital Frankfurt am Main, Frankfurt am Main, Germany;2. Consultant, Department of Oral-Craniofacial and Plastic Facial Surgery, Goethe University, Hospital Frankfurt am Main, Frankfurt am Main, Germany;3. Consultant, Department of Oral-Craniofacial and Plastic Facial Surgery, Goethe University, Hospital Frankfurt am Main, Frankfurt am Main, Germany; and Institute of Pathology, Laboratory for Regenerative Pathology and Interface Research, Johannes Gutenberg University, Mainz, Germany;4. Research Fellow, Department of Oral-Craniofacial and Plastic Facial Surgery, Goethe University, Hospital Frankfurt am Main, Frankfurt am Main, Germany;1. Department of Oral, Cranio-Maxillofacial and Facial Plastic Surgery, Medical Center of the Goethe University Frankfurt, Frankfurt am Main, Germany;2. Institute of Pathology, University Medical Center, Johannes Gutenberg University, Mainz, Germany |
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| Abstract: | BackgroundClinically, acute kidney injury (AKI) is a potentially devastating condition for which no specific therapy improves efficacy of the repair process. Bone marrow mesenchymal stromal cells (BM-MSCs) are proven to be beneficial for the renal repair process after AKI in different experimental rodent models, but their efficacy in large animals and humans remains unknown. This study aims to assess the effect of autologous rhesus Macaque mulatta monkey BM-MSC transplantation in cisplatin-induced AKI.MethodsWe chose a model of AKI induced by intravenous administration of 5 mg/kg cisplatin. BM-MSCs were transplanted through intra-arterial injection. The animals were followed for survival, biochemistry analysis and pathology.ResultsTransplantation of 5 × 106 cells/kg ameliorated renal function during the first week, as shown by significantly lower serum creatinine and urea values and higher urine creatinine and urea clearance without hyponatremia, hyperkalemia, proteinuria and polyuria up to 84 d compared with the vehicle and control groups. The superparamagnetic iron oxide nanoparticle-labeled cells were found in both the glomeruli and tubules. BM-MSCs markedly accelerated Foxp3+ T-regulatory cells in response to cisplatin-induced damage, as revealed by higher numbers of Foxp3+ cells within the tubuli of these monkeys compared with cisplatin-treated monkeys in the control and vehicle groups.ConclusionsThese data demonstrate that BM-MSCs in this unique large-animal model of cisplatin-induced AKI exhibited recovery and protective properties. |
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| Keywords: | acute kidney injury bone marrow mesenchymal stromal cells cisplatin intra-renal arterial injection |
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