BMSCs promote the differentiation of NSCs into oligodendrocytes via mediating Id2 and Olig expression through BMP/Smad signaling pathway.

Peiwen Song,Peng Ge,Cailiang Shen,Huang Fang,Ying Wang,Fulong Dong,Tianyu Han,Xiang Xia,Renjie Zhang

doi:10.1042/bsr20180303

Peiwen Song, Peng Ge + Show 7 more

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https://doi.org/10.1042/bsr20180303

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Abstract

Neural stem cells (NSCs) have emerged as a promising treatment for spinal cord injuries. However, the increasing expression of bone morphogenetic proteins (BMPs) in spinal cord injury lesion sites seems to have contributed to the limited oligodendroglial differentiation and the majority of the astroglial differentiation of NSCs. In the present study, we demonstrate that BMPs promote NSCs differentiation toward astrocytes and prevent them from differentiating into oligodendrocytes. This effect is accompanied by the increasing expression of Id2 and the reduction in Oilg1/2 expression. Treatment with bone marrow stromal cells (BMSCs) can enhance the development of oligodendrocytes in the presence of BMPs. The analysis of Id2, as well as Olig1 and Olig2 gene expression, reveals that the effect of BMPs on these gene expressions is reversed with the addition of BMSCs. In sum, these data strongly suggest that BMSCs can promote the differentiation of NSCs into oligodendrocytes through mediating Id2 and Olig1/2 expression by blocking the BMP/Smad signaling pathway.

Highlights

Spinal cord injury (SCI) is caused by direct mechanical damage to the spinal cord that induces neural cells apoptosis and demyelination of axons resulting in severe neurological functional disability that affects sensory function and mobility [1]
The results showed that the expression of both Smad1/5 and p-Smad1/5 was significantly increased by the treatment of BMP4 on the cultured neural stem cell (NSC) in comparison with the results obtained using the control medium
To help define mechanisms underlying the effects of bone marrow stromal cell (BMSC)-CM on NSCs, we examine the expression of Smad1/5, p-Smad1/5, Id2, Olig1, and Olig2 gene in the early time points (1, 6, 12, and 24 h) after exposure to BMP4 or both BMP4 and BMSC-conditioned media (BMSC-CM)

Summary

Introduction

Spinal cord injury (SCI) is caused by direct mechanical damage to the spinal cord that induces neural cells apoptosis and demyelination of axons resulting in severe neurological functional disability that affects sensory function and mobility [1]. Most studies have focused on treatments to promote neural regeneration or to replace lost neurons and neural cells [2,3]. Neural stem cells (NSCs) are capable of generating all three major central nervous system lineages (neurons, oligodendrocytes, and astrocytes) and seem to contribute to their self-repair after a SCI by replacing lost neural cells and trophic support [4,5]. A spinal cord injury induces the activation of the endogenous NSCs and leads to the robust expansion of these cells [6,7]. The effect of this spontaneous repair is inadequate because of limited oligodendroglial differentiation and the fact that a majority of the cells differentiate into astrocytes, which contributes to glial scar formation [8]. More researchers have realized that some extrinsic factors that increase or produce in a spinal cord lesion site, might be key to determining the fate of endogenous NSCs

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