C-kit(+) cells isolated from developing kidneys are a novel population of stem cells with regenerative potential

Stem Cells. 2013 Aug;31(8):1644-56. doi: 10.1002/stem.1412.

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.

Keywords: C-kit; Clonogenicity; Kidney stem cells; Multipotentiality; Regenerative potential; Self-renewal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation / physiology
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / enzymology*
  • Female
  • Kidney / cytology*
  • Kidney / embryology
  • Kidney / enzymology
  • Kidney / growth & development*
  • Kidney Cortex / cytology
  • Kidney Cortex / enzymology
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction

Substances

  • Proto-Oncogene Proteins c-kit