#4708 RENAL ORGANOID FROM URINE-DERIVED HUMAN ADULT RENAL PROGENITOR CELLS CAN SPONTANEOUSLY GENERATE LONG RENAL TUBULES

Abstract Background and Aims Organoids are self-organizing 3D aggregations of cells that represent the structure function organs. Kidney organoids have potential to advance field nephrology by providing a tool for study human kidney development disease, in vitro drug screening, ultimately, regenerative therapy. They can be derived from embryonic stem or induced pluripotent cells. We aimed explore first time, potentiality adult renal progenitor (ARPCs), isolated urine healthy subjects patients, generate spheroids purpose. Method ARPCs were immunolabeling. Optical microscopy, immunofluorescence experiments cytofluorimetric analysis used characterize organoids. CD133, NANOG, SSA4, OCT 3-4 GATA-3, SOX2 stemness marker antibodies CD13, Lotus tetragonolobus lectin, ZO-1, uromodulin, aminopeptidase investigate tubular markers. PKH26 was cell migration tubules. Real-time PCR gene expression data aquaporin profile Chick embryo chorioallantoic membrane (CAM) assays as vivo model angiogenesis. Results CKD patients. Usually, generated using complicate induction protocols with several chemical factors. However, time we under culture conditions without any stimulation, such chemokines growth factors, starting subject urine. showed express high levels markers CD133 functional constitutional ARPCs, normally low not at all expressed typical cells: SSEA4, Sox2. Moreover, able induce angiogenesis when implanted chick membrane. The urine-derived CD133+ spontaneously long tubules 6–12 days, tagging. positive proximal tubule CD13 (aminopeptidase N), lectin ZO-1. A (CD249) is present glomeruli kidneys catalyzed conversion Angiotensin II III witch important local regulation blood pressure. Also uromodulin It epithelial thick ascending limb Henle's loop, after proteolytical cleavage, secreted into In addition, genes AQP1 channel protein facilitates flow water molecules descending loop Henle; γGlut enzyme transport amino acids across membranes; Na/H exchanger 1 (SLC9A1), transporter involved pH homeostasis, volume; Na/Gluc-1 co-transporter SGLUT1, which promotes passage glucose some cases, structures similar found nephrons, including convoluted tubule, Loop Henle, Distal Convoluted collecting duct, shown optical microscopy. Conclusion For demonstrated patients these generate, spontaneously, specific portions These results open new perspectives medicine