Spinal cord injury (SCI) represents one of the most complicated and heterogeneous pathological processes of central nervous system (CNS) impairments, which is still beyond functional regeneration. Transplantation of mesenchymal stem cells (MSCs) has been shown to promote the repair of the injured spinal cord tissues in animal models, and therefore, there is much interest in the clinical use of these cells. However, many questions which are essential to improve the therapy effects remain unanswered. For instance, the functional roles and related molecular regulatory mechanisms of MSCs in vivo are not yet completely determined. It is important for transplanted cells to migrate into the injured tissue, to survive and undergo neural differentiation, or to play neural protection roles by various mechanisms after SCI. In this review, we will focus on some of the recent knowledge about the biological behavior and function of MSCs in SCI. Meanwhile, we highlight the function of biomaterials to direct the behavior of MSCs based on our series of work on silk fibroin biomaterials and attempt to emphasize combinational strategies such as tissue engineering for functional improvement of SCI.

Mesenchymal stem cells (MSCs) have the potential to treat various tissue damages, but the very limited number of cells that migrate to the damaged region strongly restricts their therapeutic applications. Full understanding of mechanisms regulating MSC migration will help to improve their migration ability and therapeutic effects. Increasing evidence shows that microRNAs play important roles in the regulation of MSC migration. In the present study, we reported that miR-9-5p was upregulated in hepatocyte growth factor -treated MSCs and in MSCs with high migration ability. Overexpression of miR-9-5p promoted MSC migration, whereas inhibition of endogenous miR-9-5p decreased MSC migration. To elucidate the underlying mechanism, we screened the target genes of miR-9-5p and report for the first time that CK1α and GSK3β, two inhibitors of β-catenin signaling pathway, were direct targets of miR-9-5p in MSCs and that overexpression of miR-9-5p upregulated β-catenin signaling pathway. In line with these data, inhibition of β-catenin signaling pathway by FH535 decreased the miR-9-5p-promoted migration of MSCs, while activation of β-catenin signaling pathway by LiCl rescued the impaired migration of MSCs triggered by miR-9-5p inhibitor. Furthermore, the formation and distribution of focal adhesions as well as the reorganization of F-actin were affected by the expression of miR-9-5p. Collectively, these results demonstrate that miR-9-5p promotes MSC migration by upregulating β-catenin signaling pathway, shedding light on the optimization of MSCs for cell replacement therapy through manipulating the expression level of miR-9-5p.