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Oligodendrocyte progenitor cells (OPCs) transplantation has been considered a promising treatment for spinal cord injury, according to previous studies. Recent research shed light on the importance of microRNA 219 (miR-219) in oligodendrocyte development, so here miR-219-overexpressing OPCs (miR-219 OPCs) were transplanted in animal models of spinal cord injury to evaluate the impact of miR-219 on oligodendrocyte differentiation and functional recovery in vivo. Our findings demonstrate that transplanted cells were distributed in the tissue sections and contributed to reducing the size of cavity in the injury site. Interestingly, miR-219 promoted OPC differentiation into mature oligodendrocyte expressing MBP in vivo whereas in absence of miR-219, less number of cells differentiated into mature oligodendrocytes. An eight week evaluation using the Basso Beattie Bresnahan (BBB) locomotor test confirmed improvement in functional recovery of hind limbs. Overall, this study demonstrated that miR-219 promoted differentiation and maturation of OPCs after transplantation and can be used in cell therapy of spinal cord injury.