Noggin Protein can Induce the Differentiation of Rat Bone Marrow Mesenchymal Stem Cells to Neurons and Repair Spinal Cord Injury.

ABSTRACT

BACKGROUND: Addressing spinal cord injury (SCI) through stem cell therapy is currently at the forefront of medical research despite its complexity. In this study, we investigated the potential of the Noggin protein in promoting the differentiation of rat bone marrow mesenchymal stem cells (BMSCs) into neuronal cells. We transplanted induced cells into a rat model with spinal cord injury. This exploration proposes an innovative perspective on stem cell therapies for spinal cord injuries. METHODS: Rat BMSCs were isolated utilizing the bone marrow cell apposition method; The multidirectional differentiation of rat BMSCs was identified by lipid induction and osteogenic induction; Rat BMSCs were induced by different concentrations of Noggin protein and different induction times; Nissel staining was used to identify the induced neuronal-like cells; The expression of synaptic protein Ⅰ (SYN1), glial fibrillary acidic protein (GFAP), and neurofilament protein 200 (NF200) in neuron-like cells was detected by immunofluorescence assay. Rats were randomly divided into a control group and a neuron-like cell group; A rat spinal cord injury model was produced, and neuron-like cells obtained from induction were transplanted into the rat's SCI. The recovery of the rats' hind limbs' motor function was detected by the Basso, Beattie, and Bresnahan (BBB) scores, and the changes in the expression of NF200 mRNA at the spinal cord injury were detected by quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: Our cultured rat BMSCs had a long spindle-shaped morphology and stained positively for oil red O after lipogenic induction and modified alizarin red S after osteogenic induction. Nissel staining of cells obtained from rat BMSCs induced by Noggin protein was positive. Immunofluorescence results showed that the induced neuronal-like cells positively expressed NF200 and SYN1, and negatively expressed GFAP. After local transplantation of induced neuronal-like cells in the rat SCI model, the BBB scores in the neuron-like cell group were higher than those in the control group at 1 w, 2 w, and 4 w, with statistically different results (p < 0.05). According to qRT-PCR results, NF200 at the spinal cord injury in the neuron-like cell group was higher than that in the control group at 12 h, 3 d, 1 w, 2 w, and 4 w, with statistically significant differences in results (p < 0.05). CONCLUSIONS: Our findings indicate that Noggin protein effectively facilitates the differentiation of rat BMSCs into neuronal cells, highlighting its potential as a therapeutic agent for repairing spinal cord injuries. This study elucidates a promising avenue in stem cell research, contributing a novel approach to regenerative strategies for spinal cord injuries.