Bone marrow-derived mesenchymal stem cells expressing the bFGF transgene promote axon regeneration and functional recovery after spinal cord injury in rats

OBJECTIVE: To investigate neurological effects of transplanting bone marrow-derived mesenchymal stem cells (BMSCs) transfected with the basic fibroblast growth factor (bFGF) gene in spinal cord-injured rats. METHODS: Ninety-six male adult Sprague-Dawley rats were randomized into four groups: (1) pcDNA3.1-bFGF group; (2) pcDNA3.1 group; (3) BMSCs group; and (4) vehicle control (DMEM) group. After the rat model of acute spinal cord injury (SCI) was established, 1×10(6) BMSCs or cells transfected with pcDNA3.1-bFGF or pcDNA3.1 were injected into rats of groups 1-3. At days 1, 7, 14, and 21 after injection, the Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to evaluate recovery of motor function. Expression changes of bFGF, myelin basic protein (MBP), and NF200 were examined by immunohistochemistry. RESULTS: The BBB score of DMEM group was significantly lower than those of groups 1-3 (P<0.05), but the score of pcDNA3.1-bFGF group was significantly higher than that of BMSCs group or pcDNA3.1 group at day 14 or 21 after injection (P<0.01). The number of bFGF-positive neurons in rats of pcDNA3.1-bFGF group was significantly higher than those of groups 1-3 at any time point (P<0.05). The optical density values of NF200-positive neurons and MBP-positive MBP axons in rats of pcDNA3.1-bFGF group were significantly higher than those of groups 1-3 at day 7 or 14 after injection (P<0.05). CONCLUSIONS: bFGF gene-modified BMSCs not only effectively promoted axonal outgrowth but also enhanced recovery of neurological function after SCI in rats, and may be a good candidate to evaluate gene therapy of SCI in man.