Stem Cell Plasticity after Blastocyst Implantation

Summary

Principal Investigator: Lawrence Recht
Abstract: Several recent studies indicate that tissue-derived stem cells can not only differentiate into cells of the tissue from which they are obtained, but also those from other tissues. We have been interested in the range of differentiative capacity (which we term plasticity) of CNS derived stem cells and hypothesized that one way to assay this would be to implant these cells into blastocyts and assess incorporation into the resulting mice later in development. Our results indicate a robust incorporation of these cells into extraneural tissues including bone marrow, where they express lineage markers of differentiated hematopoietic cells, bone muscle and GI tract. We believe this model provides a unique insight into stem cell plasticity because of the high efficiency of implantation and production of apparently normal pups. We propose to follow-up our studies by addressing the following specific aims: 1) We will determine whether incorporation of stem cells into blastocysts varies as a function of stem cell subpopulation or type, we will create a retorviral library of neural stem cells to assess whether specific subpopulations exist as well as comparing neural stem cells with marrow stromal cells in their ability to incorporate into blastocysts; 2) We will determine whether incorporation of neural stem cells into other tissues renders them functional by performing bone marrow transplantation of cells obtained from chimeric pups into lethally irradiated mice and assessing whether neural stem cells can repair a embryonically lethal genetic defect in bone; and 3) We will assess whether neural stem cells retain their functional capacity to develop into olfactory interneurons after blastocyst transplantation and determine whether their implantation at the blastocyst stage can repair mice with an absence of myelin.
Funding Period: 2001-09-30 - 2006-07-31
more information: NIH RePORT

Top Publications

  1. pmc Embryonic stem cell rescue of tremor and ataxia in myelin-deficient shiverer mice
    Hoi Pang Low
    Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Neurol Sci 276:133-7. 2009
  2. pmc Murine embryonic stem cell-derived pyramidal neurons integrate into the cerebral cortex and appropriately project axons to subcortical targets
    Makoto Ideguchi
    Department of Neurology, Stanford Medical School, Stanford, California 94305, USA
    J Neurosci 30:894-904. 2010

Scientific Experts

  • Hoi Pang Low
  • Makoto Ideguchi
  • Theo D Palmer
  • Lawrence D Recht
  • James M Weimann

Detail Information

Publications2

  1. pmc Embryonic stem cell rescue of tremor and ataxia in myelin-deficient shiverer mice
    Hoi Pang Low
    Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Neurol Sci 276:133-7. 2009
    ....
  2. pmc Murine embryonic stem cell-derived pyramidal neurons integrate into the cerebral cortex and appropriately project axons to subcortical targets
    Makoto Ideguchi
    Department of Neurology, Stanford Medical School, Stanford, California 94305, USA
    J Neurosci 30:894-904. 2010
    ..Thus, these data establish that ES-derived cortical projection neurons can integrate into anatomically relevant circuits...