Combined use of low-dose 17-beta estradiol and bone marrow mesenchymal stem cell transplantation for spinal cord repair / 中国组织工程研究

ABSTRACT

BACKGROUND: Combined use of multiple interventions for different targets play superimposed or synergistic effects,which has become the current idea for spinal cord injury treatment.OBJECTIVE: To investigate the synergistic effects of low doses of 17-β estradiol combined with bone marrow mesenchymal stem cells (BMSCs) transplantation on the recovery of motor function and inflammatory reactions after spinal cord injury in rats.METHODS: The 10 of 70 male Sprague-Dawley rats served as sham group in which the spinal cord was only exposed but with no treatment, and the rest 60 rats were used to make animal models of spinal cord injury using modified Allen's method and then randomized into four groups (n=15 per group) model, estrogen, stem cell and combined treatment groups. Rats in the stem cell and combined treatment groups were given BMSCs transplantation at injured side; rats in the estrogen and combined treatment groups were given intramuscular injection of 17-β estradiol at 1 and 24 hours after modeling. At 1, 3, 5 and 7 days after modeling, rat functional recovery was evaluated by the Basso, Beatlie, Bresnahan score. The expressions of interleukin-1β and tumor necrosis factor-α in the injured spinal cord were detected by ELISA at 6, 12, 24, and 72 hours after modeling. Apoptosis in nerve cells was observed using TUNEL staining. RESULTS AND CONCLUSION: The Basso, Beatlie, Bresnahan scores were declined significantly after modeling,increased at 5 and 7 days after stem cell transplantation, estrogen treatment or their combined treatment (P < 0.05),especially in the combined treatment group (P < 0.05). The levels of interleukin-1β and tumor necrosis factor-α were elevated gradually after spinal cord injury (P < 0.05), but the levels decreased significantly at 12 and 24 hours in stem cell,estrogen and combined treatment groups (P < 0.05), and this decrease trend was more significant in the combined treatment group compared with the stem cell and estrogen groups (P < 0.05). At 72 hours after modeling, the rate of TUNEL positive cells was highest in the model group (P < 0.05) and lowest in the combined treatment group (P < 0.05).To conclude, the combined use of low doses of 17-β estradiol and BMSCs transplantation can facilitate the recovery of motor function after spinal cord injury by effectively inhibiting apoptosis in nerve cells.