The Effect of Recombinant Tyrosine Hydroxylase Expression on the Neurogenic Differentiation Potency of Mesenchymal Stem Cells

Abstract

ObjectiveTyrosine hydroxylase (TH) is a rate-limiting enzyme in dopamine synthesis, making the enhancement of its activity a target for ensuring sufficient dopamine levels. Rat bone marrow mesenchymal stem cells (rBM-MSCs) are known to synthesize TH after differentiating into neuronal cells through chemical induction, but the effect of its ectopic expression on these cells has not yet been determined. This study investigated the effects of ectopic recombinant TH expression on the stemness characteristics of rBM-MSCs. MethodsAfter cloning, a cell line with stable TH expression was maintained, and the proliferation, the gene expression profile, and differentiation potential of rBM-MSCs were analyzed. Analysis of the cells showed an increment in the proliferation rate that could be reversed by the neutralization of TH. ResultsThe constitutive expression of TH in rBM-MSCs was successfully implemented, without significantly affecting their osteogenic and adipogenic differentiation potential. TH expression improved the expression of other neuronal markers, such as glial fibrillary acidic protein, β-tubulin, nestin, and c-Fos, confirming the neurogenic differentiation capacity of the stem cells. The expression of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) significantly increased after the chemical induction of neurogenic differentiation. ConclusionIn this study, the expression of recombinant TH improved the neuroprotective effect of MSCs by upregulating the expression of BDNF and CNTF. Although the neuronal markers were upregulated, the expression of recombinant TH alone in rBM-MSCs was not sufficient for MSCs to differentiate into neurogenic cell lines.

Impact of the Epigenetically Regulated Hoxa-5 Gene in Neural Differentiation from Human Adipose-Derived Stem Cells

“…Immunofluorescence and quantitative RT-PCR analyses demonstrated an effective process of neuronal lineage induction of hASCs, especially after treatment with the Neu1 medium. In fact, the expression of TAU and TH, two mature neuronal markers, was increased in differentiated hASCs [ 49 ]. This last, TH, has been detected as an unequivocal sign of hASCs maturation towards dopaminergic cells [ 27 ].…”

The Effect of Drag Force and Flow Rate on Mesenchymal Stem Cells in Packed-Bed Perfusion Bioreactor

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Mixed exposure to As, Mn, and Pb and dopamine neurotransmission in the striatum ‎

“…Numerous studies have reported that exposure to these metals is toxic to the central nervous system and that disturbances in dopaminergic neurotransmission are important to the development of neurotoxicity [3][4][5][6]. Dopamine regulates various aspects of brain function and is synthesized by tyrosine hydroxylase (TH) [7,8]. During dopaminergic neurotransmission, extracellular dopamine secreted into the synaptic cleft is transported by the dopamine transporter (DAT).…”