The effects of exposure of human bone marrow-derived mesenchymal stem cells to a pulsed 60 Hz magnetic field (PEMF) on cell viability and neuronal differentiation and underlying mechanisms of action should be investigated.
The study was conducted in view of a possible future use of PEMF in neurological diseases.
Cells were treated with differentiation medium (DMEM/F12 with 1 µM valproic acid, 2 µM forskolin, 2 µM butylated hydroxyanisole and 1 µM hydrocortisone) prior to exposure to the magnetic field.
Cells were also treated with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 to investigate the effect of the magnetic field on protein kinase B pathway activation and regulation of BAD phosphorylation and with the inhibitor k252a of the TrkA receptor to investigate its involvement in signal transduction.
| Exposure | Parameters |
|---|---|
|
Exposure 1:
60 Hz
Modulation type:
pulsed
Exposure duration:
up to 24 hours
|
|
| Frequency | 60 Hz |
|---|---|
| Type | |
| Waveform |
|
| Exposure duration | up to 24 hours |
| Modulation type | pulsed |
|---|
| Exposure source | |
|---|---|
| Chamber | cell culture incubator at 5% CO2 and 37°C |
| Setup | Helmholtz coils (15 inner diameter) in incubator |
| Sham exposure | A sham exposure was conducted. |
| Additional info | (remark EMF-Portal: results are given for exposure durations up to 24 hours only though longer exposure durations are mentioned in the methods) |
| Measurand | Value | Type | Method | Mass | Remarks |
|---|---|---|---|---|---|
| magnetic flux density | 10 mT | - | measured | - | - |
Cell viability and the ratio of living/apoptotic cells were significantly increased after 24 h of exposure to the magnetic field compared to the control group.
The gene expressions and/or protein expressions of neural markers NF-L, NeuroD1, Tau and MAP2 were significantly increased in exposed cells compared to the control group.
Exposure to the magnetic field also significantly increased the activity of protein kinase B (Akt), Rsk, CREB, ERK, Bcl-xL and BAD via phosphorylation. Pretreatment with the PI3K inhibitor LY294002 reversed the cell viability-enhancing effect of the magnetic field.
These results suggested that the cell-protective effect of PEMF was mediated by the PI3K/Akt/BAD pathway and that the neuronal differentiating effect was based on the CREB/ERK/Rsk pathway. The TrkA receptor can activate both signal pathways and there was a significantly increased TrkA protein expression in PEMF-exposed cells compared to the control group. When using the TrkA inhibitor K252a in PEMF exposed cells, the protein expression of phosphorylated protein kinase B (Akt) was also decreased, indicating an association.
The authors conclude that exposure of human bone marrow-derived mesenchymal stem cells to a pulsed 60 Hz magnetic field might enhance cell survival and induce neuronal differentiation via activation of the TrkA receptor and two different signal pathways. This result might be beneficial for future work on cell transplantation therapy for neurological diseases.
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