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.