title: C-kit(+) cells isolated from developing kidneys are a novel population of stem cells with regenerative potential.
abstract: 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.
authors.affiliation: Interdisciplinary Stem Cell Institute, São Paulo, São Paulo, Brazil; Sociedade Beneficente Albert Einstein, Albert Einstein Hospital, São Paulo, São Paulo, Brazil; Division of Nephrology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Erika B
authors.initials: EB
authors.lastname: Rangel
authors.forename: Samirah A
authors.initials: SA
authors.lastname: Gomes
authors.forename: Raul A
authors.initials: RA
authors.lastname: Dulce
authors.forename: Courtney
authors.initials: C
authors.lastname: Premer
authors.forename: Claudia O
authors.initials: CO
authors.lastname: Rodrigues
authors.forename: Rosemeire M
authors.initials: RM
authors.lastname: Kanashiro-Takeuchi
authors.forename: Behzad
authors.initials: B
authors.lastname: Oskouei
authors.forename: Decio A
authors.initials: DA
authors.lastname: Carvalho
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiser
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000201:enzymology*; D005260:Female; D007668:Kidney / Q000166:cytology* / Q000196:embryology / Q000201:enzymology / Q000254:growth & development*; D007672:Kidney Cortex / Q000166:cytology / Q000201:enzymology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D019009:Proto-Oncogene Proteins c-kit
keywords: C-kit; Clonogenicity; Kidney stem cells; Multipotentiality; Regenerative potential; Self-renewal