Gene therapy of spinal cord injury using gene-modified Bone Marrow Stromal Cells with Fibromodulin expressing adenoviral vector in a rat SCI model

Background Spinal cord injury (SCI) can lead to various pathological changes which create an inappropriate environment for repair. The most important of such changes are glial scar and inhibition of neuronal growth in the injured site. Exogenous administration of genes that enhance neuronal survival, synaptic plasticity, and neurotransmission has been considered as a potential approach for treating SCI. Fibromodulin is one of those genes which can decrease TGF-β1 and increase MMP-2 expression, and consequently leads to a reduction in the glial scar, promotes the growth of axons, macrophage activation, and elimination of physical and molecular barriers of neuronal growth that will end with improvement in motor performance. Moreover, bone marrow stromal cells (BMSCs) can be a promising therapeutic strategy for SCI because they can secrete neural growth factors as well as differentiate into neurons. Methods We randomly divided rats into four groups, each consisting of thirteen rats. The first group was administered normal saline, the second group received BMSCs, the third group received BMSCs infected with a beta-galactosidase expressing adenoviral vector, and the fourth group received BMSCs infected with a Fibromodulin expressing adenoviral vector. After inducing spinal cord injury using the weight-dropping method under general anesthesia, BMSCs were injected on the fourth-day post-injury. A Basso, Beattie, and Bresnahan (BBB) score test was conducted for six weeks. At the end of the fourth week, biotin dextran amine (BDA) was intracerebrally injected, and tissue staining was carried out two weeks after the injection. Results The BBB locomotor score test was applied for six weeks. There were significant differences in BBB locomotor scale between the first and the fourthgroups. The mean score of the first group in the sixth week was 5.60, while it was 9.60 for the fourth group. There were significant differences in axon counting between the groups (P<0.000). The average number of axons counted from the first to the fourth group was 87.07, 466.33, 474.13, and 829.40, respectively. Conclusions Consequently, our results highlight the therapeutic potential of the Fibromodulin expressing BMSCs for treating SCI.