De novo SIX2 activation in human kidneys treated with neonatal kidney stem/progenitor cells
| Autor: | Fanny Oliveira Arcolino, Sarah Hosgood, Sara Akalay, Nina Jordan, Jean Herman, Tegwen Elliott, Koenraad Veys, Kurt Vermeire, Ben Sprangers, Michael Nicholson, Lambertus van den Heuvel, Elena Levtchenko |
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| Přispěvatelé: | Arcolino, Fanny Oliveira [0000-0003-2207-9699], Hosgood, Sarah [0000-0002-8039-143X], Akalay, Sara [0000-0003-4398-2166], Jordan, Nina [0000-0002-6098-6751], Herman, Jean [0000-0002-6774-1685], Elliott, Tegwen [0000-0003-2041-9813], Veys, Koenraad [0000-0002-5429-111X], Vermeire, Kurt [0000-0003-1123-1907], Sprangers, Ben [0000-0003-1314-9675], Nicholson, Michael [0000-0001-7620-0664], van den Heuvel, Lambertus [0000-0003-3917-6727], Levtchenko, Elena [0000-0002-8352-7312], Apollo - University of Cambridge Repository |
| Rok vydání: | 2022 |
| Předmět: |
basic (laboratory) research/science
nephrology basic (laboratory) research kidney transplantation regenerative medicine kidney transplantation/nephrology Nerve Tissue Proteins immunosuppression/immune modulation tissue injury and repair Kidney RENAL REPAIR MESENCHYMAL STEM-CELLS All institutes and research themes of the Radboud University Medical Center stem cells stem cells organ perfusion and preservation INJURY Immunology and Allergy Humans Pharmacology (medical) science Homeodomain Proteins Transplantation Science & Technology immunosuppression immune modulation organ perfusion and preservation Stem Cells Infant Newborn EPITHELIAL-CELLS Nephrons Perfusion Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] Surgery Life Sciences & Biomedicine |
| Zdroj: | American Journal of Transplantation, 22, 12, pp. 2791-2803 American Journal of Transplantation, 22, 2791-2803 |
| ISSN: | 1600-6135 |
| Popis: | During development, nephron structures are derived from a SIX2+ stem cell population. After 36 weeks of gestation, these cells are exhausted, and no new nephrons are formed. We have previously described a non-invasive strategy to isolate and expand the native SIX2+ kidney stem cells from the urine of preterm neonates, named neonatal kidney stem/progenitor cells (nKSPC). Here, we investigated the safety and feasibility of administering nKSPC into human kidneys discarded for transplantation during normothermic machine perfusion (NMP) and evaluated the regenerative and immunomodulatory potential of nKSPC treatment. We found that nKSPC administration during NMP is safe and feasible. Interestingly, nKSPC induced the de novo expression of SIX2 in proximal tubular cells of the donor kidneys and upregulated regenerative markers such as SOX9 and VEGF. This is the first time that SIX2 re-expression is observed in adult human kidneys. Moreover, nKSPC administration significantly lowered levels of kidney injury biomarkers and reduced inflammatory cytokine levels via the tryptophan-IDO-kynurenine pathway. In conclusion, nKSPC is a novel cell type to be applied in kidney-targeted cell therapy, with the potential to induce an endogenous regenerative process and immunomodulation. ispartof: AMERICAN JOURNAL OF TRANSPLANTATION vol:22 issue:12 pages:2791-2803 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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