Contribution of human amniotic fluid stem cells to renal tissue formation depends on mTOR

Hum Mol Genet. 2010 Sep 1;19(17):3320-31. doi: 10.1093/hmg/ddq236. Epub 2010 Jun 11.

Abstract

Human amniotic fluid stem cells (hAFSCs) can be grown in large quantities, have a low risk for tumour development and harbour a high differentiation potential. They are a very promising new fetal stem cell type for cell-based therapy approaches and for studying differentiation processes without raising the ethical concerns associated with embryonic stem cells. Recently, a protocol for studies on renal development has been established in which murine embryonic kidneys are dissociated into single-cell suspension and then reaggregated to form organotypic renal structures. Using this approach, we formed chimeric renal structures via mixing murine embryonic kidney cells with monoclonal hAFSCs. We demonstrate here that hAFSCs harbour the potential to contribute to renal tissue formation accompanied by induction of specific renal marker expression. As part of the two kinase complexes mTORC1 and mTORC2, mammalian target of rapamycin (mTOR) is the key component of an important signalling pathway, which is involved in the regulation of differentiation and in the development of a wide variety of human genetic diseases many with characteristic kidney symptoms. Modulating endogenous mTOR activity via specific siRNA approaches revealed that contribution of hAFSCs to renal tissue formation is regulated by mTORC1 and mTORC2. These findings (i) demonstrate renal differentiation potential of hAFSCs, (ii) prove chimeric cultures of mixtures of murine embryonic kidney cells and hAFSCs to be a powerful tool to study the effects of gene knockdowns for renal structure formation and (iii) provide new insights into the role of the mTOR pathway for renal development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amniotic Fluid / cytology*
  • Amniotic Fluid / metabolism
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kidney / embryology*
  • Kidney / metabolism
  • Male
  • Mice
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • TOR Serine-Threonine Kinases
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Crtc1 protein, mouse
  • Crtc2 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Trans-Activators
  • Transcription Factors
  • MTOR protein, human
  • mTOR protein, mouse
  • Protein Serine-Threonine Kinases
  • TOR Serine-Threonine Kinases