Introduction: Identification of progenitor/stem cell populations in mammalian tissues is important for therapeutic applications and for understanding biological processes. We recently reported that c-Kit⁺ cells isolated from developing rat kidneys exhibit progenitor/stem cell properties. We hypothesize therefore that c-Kit⁺ cells represent a tissue-specific progenitor/stem cell population that is involved in kidney development, is maintained during adult life, and contributes to kidney regeneration. Methods: For lineage tracing, we crossed the inducible c-Kit Cre reporter mice with IRG, mT;mG, R26R LacZ, and multicolored Confetti mice. By varying the timing of tamoxifen treatment, c-Kit⁺ cells and their descendants were specifically labelled with enhanced green fluorescent protein (EGFP), LacZ or multicolor, and their spatiotemporal distribution was followed during kidney development and acute kidney injury (ischemia-reperfusion and rhabdomyolysis). Results: c-Kit expression was more abundant in early post-natal (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 through adult life, although at lower levels (5.7 in P30 and 2.2 in P90-180). When tamoxifen was administered 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 ureteric bud invades the metanephric mesenchyma, ribbons of c-Kit-EGFP/LacZ⁺ cells expanded to form tubular structures and were detected in structures resembling the S-shaped bodies. In post-natal period, the number of c-Kit-EGFP/LacZ⁺/clonal multicolored cells increased in the cortex, medulla, and papilla. In adult mice, c-Kit-EGFP/LacZ⁺/clonal multicolored cells were found in distinct renal segments (macula densa, distal tubules and collecting ducts). After acute kidney injury, the number of c-Kit⁺ clones increased from 10±3 to 36.5±8 (P<0.0001), notably in the outer medulla. Conclusions: c-Kit marks a kidney progenitor/stem cell population and may have therapeutic application.

CITATION INFORMATION: Abreu Gomes S, Goss G, Goldstein B, Seidler B, Saur D, Hare J, Bevilaqua Rangel E. c-Kit⁺ Cells Are Kidney-Specific Progenitor/Stem Cells with Regenerative Potential. Am J Transplant. 2016;16 (suppl 3).

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