Nestin+ kidney resident mesenchymal stem cells for the treatment of acute kidney ischemia injury |
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Affiliation: | 1. Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;2. Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China;3. Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;4. Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;5. Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;6. Department of Cardiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;7. Department of Geriatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;8. Department of Urology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China;9. Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China;10. Institute of Hypertension & Kidney Research, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;11. Department of Nephrology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;12. Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, China;13. Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA;1. State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China;2. University of Chinese Academy of Sciences, Beijing 100049, China;3. Department of Radiology, The Second Hospital of Jilin University, Changchun 130022, PR China;4. College of Clinical Medicine, Jilin University, Changchun, Jilin 130012, PR China;1. Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA;2. Division of Plastic and Reconstructive Surgery, Greater Los Angeles VA Healthcare System, Los Angeles, CA 90073, USA;3. Research Service, Greater Los Angeles VA Healthcare System, USA;4. Department of Chemical and Biomolecular Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA;5. Department of Pathology, Greater Los Angeles VA Healthcare System, USA;1. Department of Anatomical Sciences, School of Medical Sciences, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran;2. Shefa Neurosciences Research Center, Khatam Al-Anbia Hospital, Tehran, Iran;3. Department of Anatomy, Shahed University, Tehran, Iran;4. Department of genetics, School of Basic Sciences, Tarbiat Modares University, Tehran, Iran;5. Middle Euphrates Neuroscience Center, Kufa University,College of Medicine, Annajaf Al-Ashraf, Iraq |
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Abstract: | Renal resident mesenchymal stem cells (MSCs) are important regulators of kidney homeostasis, repair or regeneration. However, natural distribution and the starting population properties of these cells remain elusive because of the lack of specific markers. Here, we identified post-natal kidney derived Nestin+ cells that fulfilled all of the criteria as a mesenchymal stem cell. These isolated Nestin+ cells expressed the typical cell-surface marker of MSC, including Sca-1, CD44, CD106, NG2 and PDGFR-α. They were capable of self-renewal, possessed high clonogenic potential and extensive proliferation for more than 30 passages. Under appropriate differentiation conditions, these cells could differentiate into adipocytes, osteocytes, chondrocytes and podocytes. After intravenous injection into acute kidney injury mice, Nestin+ cells contributed to functional improvement by significantly decreasing the peak level of serum creatinine and BUN, and reducing the damaged cell apoptosis. Furthermore, conditioned medium from Nestin+ cells could protect against ischemic acute renal failure partially through paracrine factor VEGF. Taken together, our findings indicate that renal resident Nestin+ MSCs can be derived, propagated, differentiated, and repair the acute kidney injury, which may shed new light on understanding MSCs biology and developing cell replacement therapies for kidney disease. |
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Keywords: | Nestin MSCs Acute kidney injury Paracrine VEGF |
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