Single adult kidney stem/progenitor cells reconstitute three-dimensional nephron structures in vitro

Shinji Kitamura, Hiroyuki Sakurai, Hirofumi Makino

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The kidneys are formed during development from two distinct primordial tissues, the metanephric mesenchyme and the ureteric bud. The metanephric mesenchyme develops into the kidney nephron, the minimal functional unit of the kidney. A nephron consists of several segments and regulates water, electrolyte, and acid-base homeostasis in addition to secreting certain hormones. It has been predicted that the kidney will be among the last organs successfully regenerated in vitro due to its complex structure and multiple functions. Here, we show that adult kidney stem/progenitor cells (KS cells), derived from the S3 segment of adult rat kidney nephrons, can reconstitute a three-dimensional kidney-like structure in vitro. Kidney-like structures were formed when a cluster of KS cells was suspended in an extracellular matrix gel and cultured in the presence of several growth factors. Morphological analyses revealed that these kidney-like structures contained every substructure of the kidney, including glomeruli, proximal tubules, the loop of Henle, distal tubules, and collecting ducts, but no vasculature. Our results demonstrate that a cluster of tissue stem/progenitor cells has the ability to reconstitute the minimum unit of its organ of origin by differentiating into specialized cells in the correct location. This process differs from embryonic kidney development, which requires the mutual induction of two different populations of progenitors, metanephric mesenchymal cells and ureteric bud cells. Stem Cells 2015;33:774-784

Original languageEnglish
Pages (from-to)774-784
Number of pages11
JournalStem Cells
Volume33
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

Keywords

  • Adult kidney tissue stem cells
  • Organogenesis
  • Three-dimensional nephron structures in vitro

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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