Abstract
Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has the potential to be developed into an effective treatment for neurodegenerative diseases such as Alzheimer's disease (AD). However, the therapeutic effects of BMSCs are limited by their low neural differentiation rate. We transfected BMSCs with neurotrophin-3 (NT-3), a neurotrophic factor that promotes neuronal differentiation, and investigated the effects of NT-3 gene overexpression on the differentiation of BMSCs into neurons in vitro and in vivo. We further studied the possible molecular mechanisms. We found that overexpression of NT-3 promoted the differentiation of BMSCs into neurons in vitro and in vivo and improved cognitive function in rats with experimental AD. By contrast, silencing NT-3 inhibited the differentiation of BMSCs and decreased cognitive function in rats with AD. The Wnt/β-catenin signaling pathway was involved in the mechanism by which NT-3 gene modification influenced the neuronal differentiation of BMSCs in vitro and in vivo. Our findings support the prospect of using NT-3-transduced BMSCs for the development of novel therapies for AD.
Highlights
Neurodegenerative diseases of the central nervous system, which cause nerve cell damage and neurologic impairment, are major and debilitating medical conditions that exert great burdens on patients, their families and healthcare services
Based on the above research, we speculated that the transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) modified with the gene for NT-3 could have an impact on nerve regeneration and recovery of cognitive function that might be relevant to the treatment of Alzheimer’s disease (AD)
We evaluated the effects of NT-3 on the differentiation of BMSCs into neurons in vitro and in vivo and on the recovery of cognitive function after BMSC transplantation in a rat model of AD
Summary
Neurodegenerative diseases of the central nervous system, which cause nerve cell damage and neurologic impairment, are major and debilitating medical conditions that exert great burdens on patients, their families and healthcare services. Stem cell transplantation has received increasing attention as a novel treatment for neurodegenerative diseases of the central nervous system. There is a growing body of evidence demonstrating that NT-3 promotes the survival of Neurotrophin-3 Promotes the Neuronal Differentiation of BMSCs neurons and repair of nerves (Mo et al, 2010; Rak et al, 2014; Wang Y. et al, 2018). Previous research has suggested that the transplantation of BMSCs overexpressing NT-3 could promote recovery of locomotor function and nerve regeneration in a rat model of spinal cord injury (Wang et al, 2014). Based on the above research, we speculated that the transplantation of BMSCs modified with the gene for NT-3 could have an impact on nerve regeneration and recovery of cognitive function that might be relevant to the treatment of AD
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