Abstract
Urine has become the source of choice for noninvasive renal epithelial cells and renal stem cells which can be used for generating induced pluripotent stem cells. The aim of this study was to generate a 3D nephrogenic progenitor cell model composed of three distinct cell types—urine-derived SIX2-positive renal progenitor cells, iPSC-derived mesenchymal stem cells, and iPSC-derived endothelial cells originating from the same individual. Characterization of the generated mesenchymal stem cells revealed plastic adherent growth and a trilineage differentiation potential to adipocytes, chondrocytes, and osteoblasts. Furthermore, these cells express the typical MSC markers CD73, CD90, and CD105. The induced endothelial cells express the endothelial cell surface marker CD31. Upon combination of urine-derived renal progenitor cells, induced mesenchymal stem cells, and induced endothelial cells at a set ratio, the cells self-condensed into three-dimensional nephrogenic progenitor cells which we refer to as 3D-NPCs. Immunofluorescence-based stainings of sectioned 3D-NPCs revealed cells expressing the renal progenitor cell markers (SIX2 and PAX8), podocyte markers (Nephrin and Podocin), the endothelial marker (CD31), and mesenchymal markers (Vimentin and PDGFR-β). These 3D-NPCs share kidney progenitor characteristics and thus the potential to differentiate into podocytes and proximal and distal tubules. As urine-derived renal progenitor cells can be easily obtained from cells shed into urine, the generation of 3D-NPCs directly from renal progenitor cells instead of pluripotent stem cells or kidney biopsies holds a great potential for the use in nephrotoxicity tests, drug screening, modelling nephrogenesis and diseases.
Highlights
Many disease conditions, including renal diseases, require replacement of tissues or organs
An alternative to kidney transplantations is the use of renal progenitor cells, which can be isolated from human urine [1], in order to generate kidney cell types and subsequently transplantable renal tissues
urinederived renal progenitor cell (UdRPC)-iMSCs were successfully generated from the induced pluripotent stem cells (iPSCs) line UM51 reprogrammed from UdRPCs [17]
Summary
Many disease conditions, including renal diseases, require replacement of tissues or organs. As stem cells can be used for the generation of autologous, specialized cell types, stem cell-based therapies are an alternative to transplantation [2] Both treatments face major problems: worldwide donor shortage, poor immunohistocompatibility between the donor and recipient, and the probability of side effects such as teratoma and tumor formation upon stem cell therapy. UdRPCs have a rice grain-like morphology [3] and share stem cell characteristics including clonogenicity, high expansion capacity, multipotent differentiation potency, and self-renewal driven by SIX2 [3, 5, 6]. These cells have the potential to be differentiated into numerous cell types present within the kidney
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