Treatment Of Spinal Cord Injury In Rat With Intravenous Administration Of Bone Marrow Stromal Cells

[Subject] To measure the therapeutic efficacy for the treatment of spinal cord injury with intravenous administration of bone marrow stromal cells .[Background] Spinal cord injuries often characterized by immediate and irreversible loss of sensor and motors below the level of injury,and exact a physical, emotional and economic toll both on those who are affected and on society at large.The capacity of certain damaged axons to regeneratation and elongation in the CNS and PNS are more dependent on the enviroment in which these axons are located than intrinsic properties of neurons.Cell transplantation to repair spinal cord injury is a vibrant area of research with the goal of reducing functional deficit,which can facilitates growth of axons by serving as a celluar bridge and providing chemical and mechanical cues for injured neural processes,provides new neurons which in turn provide new targets and sources of innervation and repair damaged neural circuits, and secretes an array of factors,such as neurotrophic factors,that might aid in the repair process.Bone marrow stromal cells have been shown to be multipotent stem cell,can differentiate into microglia, astrocytes and even neuronal cells under experimental cell culture conditions in vitro and migrate and exhibit site-dependent differentiation by system infusion or directly transplantationin vivo. [Methods] (1) BMSCs wrere harvested and Isolated from additional 10 adult Sprague-Dawley rats and then cultured,purified,expanded and labeled with bromodeoxyuridine(BrdU).(2) 46 adult Sprague-Dawley rats were subjected to weight-drop impact causing complete paraplegia and then randomly divided into 3 groups 7 days after injury. 18 rats in group A was treated group, 16 in group B was controlled group and 12 in group C was sham group. (3) 2× 106 BMSC cultured in 1ml phosphate-buffered saline were infused into the rats respectively in group A by tail vein and 1 ml L-DMEM was did in group B .(4) The distribution of donor cells in spinal cord ,brain,heart,liver, lung , kidley and spleen were analyzed in recipient rats using immmonohistochemical staining and the differentiation of donor cells in contused spinal cord was did double-labeled immmonohistochemical staining. Motor function of the three groups was evaluated respectively by the Basso-Beattie-Bresnahan(BBB) scors before and at 1,7,14 21,28,35.42 days after injury . [Result] BMSC can be expanded rapidly in vitro. BMSC migrated into spinal cord,survived and exhibited site-dependent differentiation with intravenous administration after spinal cord injury. Bromodeoxyuridine-reactive cells(~4.9% of 2 × 106 injected BMSC) distributed through the contused regions of spinal cord at 14 days after injury although BMSC were also found in other organs and primarily located to around the vascular structures,12.6% bromodeoxyuridine-reactive cells expressed the astrocytic marker GAFP and 5.4% expressed the neuronal marker NeuN.The expression of growth-associatedprotein-43(GAP-43 ) ,neurofilament(NF) and the BBB score in group A was significantly higher compared to group B or group C. Nestin-reactivecells around the contused spinal cord was significantly higher compared to group B or group C at second and third weak after intravenous administration. [Conclusion] Intravenous administration of BMSC can upregulates the expressionof GAP-43 and NF,facilitates regeneration and growth of axons and promotes the proliferation of ependymal cells following spinal cord injury.It may be useful in the treatment of spinal cord injury...