Combination of Human Mesenchymal Stem Cells and Repetitive Transcranial Magnetic Stimulation Enhances Neurological Recovery of 6-Hydroxydopamine Model of Parkinsonian's Disease.

Abstract

Repetitive transcranial magnetic stimulation (rTMS) has been in use for the treatment of various neurological diseases, including depression, anxiety, stroke and Parkinson's disease (PD), while its underlying mechanism is stills unclear. This study was undertaken to evaluate the potential synergism of rTMS treatment to the beneficial effect of human mesenchymal stem cells (hMSCs) administration for PD and to clarify the mechanism of action of this therapeutic approach. The neuroprotective effect in nigral dopamine neurons, neurotrophic/growth factors and anti-/pro-inflammatory cytokine regulation, and functional recovery were assessed in the rat 6-hydroxydopamine (6-OHDA) model of PD upon administration of hMSCs and rTMS. Transplanted hMSCs were identified in the substantia nigra, and striatum. Enhancement of the survival of SN dopamine neurons and the expression of the tyrosine hydroxylase protein were observed in the hMSCs + rTMS compared to that of controls. Combination therapy significantly elevated the expression of several key neurotrophic factors, of which the highest expression was recorded in the rTMS + hMSC group. In addition, the combination therapy significantly upregulated IL-10 expression while decreased IFN-γ and TNF-α production in a synergistic manner. The treadmill locomotion test (TLT) revealed that motor function was improved in the rTMS + hMSC treatment with synergy. Our findings demonstrate that rTMS treatment and hMSC transplantation could synergistically create a favorable microenvironment for cell survival within the PD rat brain, through alteration of soluble factors such as neurotrophic/growth factors and anti-/pro-inflammatory cytokines related to neuronal protection or repair, with preservation of DA neurons and improvement of motor functions.