Combination of bone marrow mesenchymal stem cells and brain-derived neurotrophic factor for treating spinal cord injury

BACKGROUND: Because bone marrow mesenchymal stem cells (BMSCs) do not secrete sufficient brain-derived neurotrophic factor (BDNF), the use of exogenous BDNF could improve microenvironments in injured regions for BMSCs differentiation. OBJECTIVE: To analyze recovery of the injured spinal cord following BMSCs venous transplantation in combination with consecutive injections of BDNF. DESIGN, TIME AND SETTING: A randomized, controlled animal experiment was performed at the Central Laboratory of First Hospital and Anatomical Laboratory, Fujian Medical University from October 2004 to May 2006. MATERIALS: Human BDNF was purchased from Sigma, USA. METHODS: A total of 44 New Zealand rabbits were randomly assigned to model (n = 8), BONE (n = 12), BMSC (n = 12), and BMSC+BDNF (n = 12) groups. Spinal cord (L-2) injury was established with the dropping method. The model group rabbits were injected with 1 mL normal saline via the ear margin vein; the BDNF group was subdurally injected with 100 mu g/d human BDNF for 1 week; the BMSC group was injected with 1 mL BMSCs suspension (2 x 10(6)/mL) via the ear margin vein; and the BMSC+BDNF group rabbits were subdurally injected with 100 mu g/d BDNF for 1 week, in addition to BMSCs suspension via the ear margin vein. MAIN OUTCOME MEASURES: BMSCs surface markers were detected by flow cytometry. BMSCs differentiation in the injured spinal cord was detected by immunofluorescence histochemistry. Functional and structural recovery, as well as morphological changes, in the injured spinal cord were respectively detected by Tarlov score, horseradish peroxidase retrograde tracing, and hematoxylin & eosin staining methods at 1, 3, and 5 weeks following transplantation. RESULTS: Transplanted BMSCs differentiated into neuronal-like cells in the injured spinal cord at 3 and 5 weeks following transplantation. Neurological function and pathological damage improved following BMSC + BDNF treatment compared with BDNF or BMSC alone (P < 0.01 or P < 0.05). CONCLUSION: BMSCs venous transplantation in combination with BDNF subdural injection benefits neuronal-like cell differentiation and significantly improves structural and function of injured spinal cord compared with BMSCs or BDNF alone.