科研之友
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摘要
Cellular therapies using stem cells are promising approaches for the treatment of neurological diseases, as neuron has limited potential to self-renew or repair. Thus, mesenchymal stem cells (MSCs), a kind of multipotent progenitors, can represent an alternative source of cells for neuron replacement therapies. Here we show that forced co-expression of neurogenic factors Nurr1 and Mash1, two transcriptional factors specific to dopamine neuron development and treatment with Neurobasal-A medium containing nerve growth factor and GSK-3 inhibitors (TWS119) could directly and effectively induce mesenchymal stem cells differentiation into morphologically, phenotypically and functionally neuron-like cells. The differentiated cells significantly increased expression of neuron specific transcription factors (Pitx3, Lmx1a, Ngn2 and En2); increased various neuron markers such as tyrosine hydroxylase, microtubule associated protein-2 (MAP2), dopamine transporter (DAT), neuron-specific neuronal protein (NeuN), neurofilament medium (NF-M), beta-III Tubulin (Tuj1) and neuron specific enolase (NSE). Our results showed characteristic dopamine neurotransmitter release in response to depolarization stimuli and specific dopamine reuptake properties in vitro. Nurr1 and Mash1 expression remained the number of dopamine neuron-like cells stable in the cultures for 15 days, implying that Mash1 and Nurr1 modulate neuron-like differentiation of mesenchymal stem cells. Altogether, the combined expression of specific transcription factors Nurr1 and Mash1 enhances mesenchymal stem cells differentiation in vitro to generate neuron-like cells as a promising source of cell for therapy of neurological diseases.
