Generation of Induced Nephron Progenitor-like Cells from Human Urine-Derived Cells

Abstract

Background: Regenerative medicine strategies employing nephron progenitor cells (NPCs) are a viable approach that is worthy of substantial consideration as a promising cell source for kidney diseases. However, the generation of induced nephron progenitor-like cells (iNPCs) from human somatic cells remains a major challenge. Here, we describe a novel method for generating NPCs from human urine-derived cells (UCs) that can undergo long-term expansion in a serum-free condition. Results: Here, we generated iNPCs from human urine-derived cells by forced expression of the transcription factors OCT4, SOX2, KLF4, c-MYC, and SLUG, followed by exposure to a cocktail of defined small molecules. These iNPCs resembled human embryonic stem cell-derived NPCs in terms of their morphology, biological characteristics, differentiation potential, and global gene expression and underwent a long-term expansion in serum-free conditions. Conclusion: This study demonstrates that human iNPCs can be readily generated and expanded, which will facilitate their broad applicability in a rapid, efficient, and patient-specific manner, particularly holding the potential as a transplantable cell source for patients with kidney disease.

Power of pee: Urine‐derived stem cells in urological disorders

“…USCs as a subpopulation of cells isolated from urine possess biological characteristics of stem cells, that is, clonogenicity, high expansion capacity [ 2,19 ] , gene expression profiles of cell surface markers characteristic of stem cells, multipotent differentiation capacity [ 22–24 ] , particularly renal cell types such as podocytes [ 25 ] , and urothelial cells [ 26 ] , smooth muscle cells and endothelial cells with proangiogenic and neurogenic paracrine effects [ 3,18 ] , immunomodulatory properties [ 27 ] , and easily induced pluripotent stem cells [ 28–31 ] . Multiple other teams around the world have confirmed these results [ 32–44 ] and have used USCs for regeneration of bladder [ 41 ] , urethra [ 14 ] , kidney [ 32,38,45 ] , penal tissue [ 17,21 ] , bone [ 36,37,44,46 ] , lungs [ 47 ] , skin [ 48 ] , nerves [ 49 ] , and other types of tissue [ 16,20,44,46,48–54 ] .…”