Abstract: SA-PO0020
Neonatal Urine-Derived Kidney Cells from 52 Donors Reveal Kidney Progenitor and Tubular Phenotypes and Are a Novel Source of Kidney Tubular Organoids
Session Information
- Development, Stem Cells, and Regenerative Medicine
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 700 Development, Stem Cells, and Regenerative Medicine
Authors
- Lantermans, Hildo C., Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands
- Deffrennes, Sara, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
- Kraan, Willem, Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands
- Römer, Kamla Elizabeth, Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands
- Rayyan, Maissa, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
- Hermans, Isabelle, UZ Leuven, Leuven, Flanders, Belgium
- Nuytemans, Debbie H.g.m., Emma Kinderziekenhuis Amsterdam UMC, Amsterdam, NH, Netherlands
- Onland, Wes, Emma Kinderziekenhuis Amsterdam UMC, Amsterdam, NH, Netherlands
- Verhaar, Marianne C., University Medical Center Utrecht, Utrecht, NH, Netherlands
- Slaats, Gisela G., University Medical Center Utrecht, Utrecht, NH, Netherlands
- Van den Heuvel, Lambertus P.W.J., Radboud universitair medisch centrum, Nijmegen, GE, Netherlands
- Florquin, Sandrine, Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands
- Devos, Timothy, UZ Leuven, Leuven, Flanders, Belgium
- Arcolino, Fanny Oliveira, Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands
- Levtchenko, Elena, Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands
Background
We previously described the in vitro expansion of SIX2+ cells from the urine of preterm neonates. These cells exhibit features of nephron progenitor cells (NPC), including NPC markers and multilineage differentiation potential. Furthermore, these cells potentially induce regeneration in ex vivo machine perfusion. Building on these findings, we aimed to set up a biobank of neonatal urine-derived kidney cells (nuKC) across gestational ages (GA) and determine their potential for regenerative medicine and in vitro modelling.
Methods
Urine samples were collected from 52 newborns with GA ranging from 24w to >37w and analyzed for cell growth, transcriptional profile and their potential to form kidney tubular organoids (tubuloids).
Results
Forty out of 52 samples showed cell growth (76.9%) with 38 % expressing the NPC marker SIX2, independent of GA or sex. SIX2+ nuKC proliferated for at least 10 passages (>2 months), most continued beyond 20 passages with stable doubling time. Single cell analysis from 14 nuKC showed that SIX2+ populations formed distinct clusters irrespective of GA or donor. These clusters show differential expression of cap mesenchyme markers, including SIX2, WT1, TMEM100, HOXB9 and MFAP4, supporting an NPC-like identity. In contrast, SIX2- clusters expressed genes consistent with committed kidney epithelial lineages, such as the proximal tubule, Loop of Henle and collecting duct. Furthermore, 67 % of the tested nuKC formed kidney tubular organoids. The potency to form tubuloids was remarkably higher for nuKC resembling committed kidney epithelial lineages, compared to an NPC-like transcriptomic identity. Importantly, we showed that nuKC can easily be genetically modified prior to tubuloid formation, allowing for the generation of isogenic tubuloids modeling genetic kidney disease.
Conclusion
Our results show that the isolation and expansion of nuKC is highly efficient, with a substantial proportion expressing SIX2. Single-cell transcriptomics demonstrated that, independent of GA, SIX2+ cells form a distinct NPC-like cluster, whereas SIX2- cells exhibit profiles of more committed kidney lineages and are a novel source of tubuloids, suited for modeling genetic kidney disease. Taken together, the resulting nuKC biobank represents a valuable resource for kidney regenerative therapy and 3D genetic disease modeling.
Funding
- Private Foundation Support