Lineage Tracing Identifies C-Kit Cells as a Population of Kidney-Specific Stem Cells during Development and in Acute and Chronic Kidney Diseases
1Albert Einstein Hospital, São Paulo, Brazil, 2University of Miami, Miami, FL, 3Medizinische Klinik, Technische Universität München, Munich, Germany, 4University of São Paulo, São Paulo, Brazil
Meeting: 2019 American Transplant Congress
Abstract number: 593
Keywords: Kidney, Mice, Renal injury, Stem cells
Session Information
Session Name: Concurrent Session: Stem Cell, Cellular Therapies and Regenerative Medicine
Session Type: Concurrent Session
Date: Tuesday, June 4, 2019
Session Time: 4:30pm-6:00pm
Presentation Time: 4:42pm-4:54pm
Location: Room 310
*Purpose: We recently reported that c-Kit cells isolated from developing kidneys exhibit regenerative potential in mouse models of acute nephrotic syndrome and ischemia-reperfusion injury. These cells have already been isolated from human deceased donors. We hypothesize therefore that c-Kit cells represent a kidney-specific stem population that is involved in kidney development and is maintained throughout adult life, as verified by lineage tracing studies in vivo.
*Methods: We crossed the inducible c-Kit reporter (c-KitCreERT2/+) mice with IRG, mT;mG, LacZ, multicolored Confetti, BTBRob/ob mice. By varying the time of tamoxifen treatment, c-Kit cells and their descendants were specifically labelled with enhanced green fluorescent protein (EGFP), LacZ, or multicolour fluorescence. So, their spatiotemporal distribution was followed during kidney development and acute (ischemia-reperfusion and rhabdomyolysis) and chronic (diabetic nephropathy) kidney injury.
*Results: c-Kit expression was more abundant in early postnatal (P) period (7.91 in P0.5-3.5; 10.6 in P7-14 vs 3.13 in embryonic [E]17.5-18.5 (P<0.0001), and was maintained throughout adult life, yet at lower levels (5.7 in P30 and 2.2 in P90-180). When tamoxifen was injected during E7.5-9.5, a few EGFP/LacZ+ cells were observed in tubular segments from cortex to medulla, and at E10.5-12.5, when metanephros development initiates, ribbons of c-Kit-EGFP/LacZ+ cells expanded to form tubular structures that resembled S-shaped bodies. In postnatal period, the number of c-Kit-EGFP/LacZ/clonal multicolour cells increased in the cortex, medulla, and papilla, where they were found in proximal and distal tubules, collecting ducts, and podocytes. In adult mice, these cells were found in distinct segments, including co-localization with calbindin-D28K (distal tubules) and AQP2 (collecting ducts). After acute injury, the number of c-Kit clones increased from 10±3 to 36.5±8 (P<0.0001) in the outer medulla. In the c-Kit;mTmG;BTBR ob/ob mice, a robust model of diabetic nephropathy, we found on average 21±3 glomeruli that exhibit c-Kit-EGFP cells in these mice (versus 12.2±2.2 glomeruli in heterozygous mice; P=0.035) and also 2.43±0.3 c-Kit-EGFP positve cells/glomerulus (vs 1.6±0.2; P=0.038).
*Conclusions: These novel findings have important implications for the advancement of cell therapy for acute and chronic kidney diseases.
To cite this abstract in AMA style:
Rangel EB, Higuti-Sousa E, Goss G, Goldstein B, Seidler B, Saur D, Gomes SA, Hare JM. Lineage Tracing Identifies C-Kit Cells as a Population of Kidney-Specific Stem Cells during Development and in Acute and Chronic Kidney Diseases [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/lineage-tracing-identifies-c-kit-cells-as-a-population-of-kidney-specific-stem-cells-during-development-and-in-acute-and-chronic-kidney-diseases/. Accessed May 18, 2025.« Back to 2019 American Transplant Congress