C-Kit(+) Cells Isolated from Developing Kidneys Are a Novel Population of Stem Cells with Regenerative Potential

The presence of tissue specific precursor cells is an emerging concept in organ formation and tissue homeostasis. Several progenitors are described in the kidneys. However, their identity as a true stem cell remains elusive. Here, we identify a neonatal kidney-derived c-kit(+) cell population that fulfills all of the criteria as a stem cell. These cells were found in the thick ascending limb of Henle's loop and exhibited clonogenicity, self-renewal, and multipotentiality with differentiation capacity into mesoderm and ectoderm progeny. Additionally, c-kit(+) cells formed spheres in nonadherent conditions when plated at clonal density and expressed markers of stem cells, progenitors, and differentiated cells. Ex vivo expanded c-kit(+) cells integrated into several compartments of the kidney, including tubules, vessels, and glomeruli, and contributed to functional and morphological improvement of the kidney following acute ischemia-reperfusion injury in rats. Together, these findings document a novel neonatal rat kidney c-kit(+) stem cell population that can be isolated, expanded, cloned, differentiated, and used for kidney repair following acute kidney injury. These cells have important biological and therapeutic implications. STEM Cells 2013;31:1644-1656

James and Esther King Florida Biomedical Research Program

National Institutes of Health

Univ Miami, Leonard M Miller Sch Med, Interdisciplinary Stem Cell Inst, Miami, FL 33136 USA

Univ Miami, Leonard M Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA

Univ Miami, Leonard M Miller Sch Med, Dept Surg, Miami, FL 33136 USA

Univ Miami, Leonard M Miller Sch Med, Dept Pathol, Miami, FL 33136 USA

Univ Miami, Leonard M Miller Sch Med, Div Nephrol & Hypertens, Miami, FL 33136 USA

Univ Miami, Leonard M Miller Sch Med, Div Cardiol, Dept Med, Miami, FL 33136 USA

Albert Einstein Hosp, Soc Beneficente Albert Einstein, São Paulo, Brazil

Universidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil

Universidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil

James and Esther King Florida Biomedical Research Program: 1KD07-33958

National Institutes of Health: HL107110

National Institutes of Health: AG025017

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