Transcranial Magnetic Stimulation of Human Adult Stem Cells in the Mammalian Brain

Front Neural Circuits. 2016 Mar 17:10:17. doi: 10.3389/fncir.2016.00017. eCollection 2016.

Abstract

Introduction: The burden of stroke on the community is growing, and therefore, so is the need for a therapy to overcome the disability following stroke. Cellular-based therapies are being actively investigated at a pre-clinical and clinical level. Studies have reported the beneficial effects of exogenous stem cell implantation, however, these benefits are also associated with limited survival of implanted stem cells. This exploratory study investigated the use of transcranial magnetic stimulation (TMS) as a complementary therapy to increase stem cell survival following implantation of human dental pulp stem cells (DPSC) in the rodent cortex.

Methods: Sprague-Dawley rats were anesthetized and injected with 6 × 10(5) DPSC or control media via an intracranial injection, and then received real TMS (TMS0.2 Hz) or sham TMS (TMSsham) every 2nd day beginning on day 3 post DPSC injection for 2 weeks. Brain sections were analyzed for the survival, migration and differentiation characteristics of the implanted cells.

Results: In animals treated with DPSC and TMS0.2 Hz there were significantly less implanted DPSC and those that survived remained in the original cerebral hemisphere compared to animals that received TMSsham. The surviving implanted DPSC in TMS0.2 Hz were also found to express the apoptotic marker Caspase-3.

Conclusions: We suggest that TMS at this intensity may cause an increase in glutamate levels, which promotes an unfavorable environment for stem cell implantation, proliferation and differentiation. It should be noted that only one paradigm of TMS was tested as this was conducted as a exploratory study, and further TMS paradigms should be investigated in the future.

Keywords: dental pulp stem cells; glutamate; rat; stroke; transcranial magnetic stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / drug effects
  • Adult Stem Cells / radiation effects*
  • Adult Stem Cells / transplantation
  • Analysis of Variance
  • Animals
  • Brain / drug effects
  • Brain / physiology*
  • Brain / surgery
  • Caspase 3 / metabolism
  • Cell Count
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Dental Pulp / cytology
  • Dose-Response Relationship, Drug
  • Glutamic Acid / pharmacology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Male
  • Nerve Tissue Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transcranial Magnetic Stimulation*
  • Transduction, Genetic
  • Up-Regulation / radiation effects

Substances

  • Nerve Tissue Proteins
  • Green Fluorescent Proteins
  • Glutamic Acid
  • Caspase 3