De novo SIX2 activation in human kidneys treated with neonatal kidney stem/progenitor cells. Issue 12 (11th August 2022)

• Record Type: Journal Article
• Authors: Arcolino, Fanny Oliveira; Hosgood, Sarah; Akalay, Sara; Jordan, Nina; Herman, Jean; Elliott, Tegwen; Veys, Koenraad; Vermeire, Kurt; Sprangers, Ben; Nicholson, Michael; van den Heuvel, Lambertus; Levtchenko, Elena
• Is Part Of: American journal of transplantation. Volume 22:Issue 12(2022)
• Page Start: 2791
• Page End: 2803
• Publication Date: 2022-08-11
• Subjects: basic (laboratory) research/science -- immunosuppression/immune modulation -- kidney transplantation/nephrology -- regenerative medicine -- stem cells, organ perfusion and preservation -- tissue injury and repair; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.17164
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : 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. Abstract : In human discarded kidneys, administration of neonatal kidney stem/progenitor cells during normothermic machine perfusion exerts immunomodulatory effects and induces de novo expression of a developmental transcription factor and markers of regeneration in proximal tubular cells.