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 × 105 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.
Highlights
The burden of stroke on the community is growing, and so is the need for a therapy to overcome the disability following stroke
At 3 h post-plating, cells were incubated with various concentrations of Glutamate (Sigma, G1251) for either 15 min to simulate the up-regulation of glutamate seen during transcranial magnetic stimulation (TMS), 24 h or one trial where glutamate was added for 15 min, followed by a washout step for 45 min with the addition of glutamate and washout was repeated for a total of six times to replicate the in vivo paradigm of TMS used with each experiment completed in triplicate
1www.rockland-inc.com 2www.abcam.com 3www.cellsignal.com 4www.invitrogen.com the total number of green fluorescent protein (GFP) expressing dental pulp stem cells (DPSC) from all five sections in animals treated with real TMS0.2 Hz or TMSsham
Summary
The burden of stroke on the community is growing, and 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, these benefits are 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. Brain sections were analyzed for the survival, migration and differentiation characteristics of the implanted cells
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