Spinal cord injury (SCI) is a significant clinical challenge and,to date,no effective treatment is available.Oligodendrocyte progenitor cell (OPC) transplantation has been a promising strategy for SCI repair;however,the poor post-transplantation survival and deficiency in differentiation into myelinating oligodendrocytes (OLs) are two major challenges,which limit their use as donor cells.Here we report the generation of a relatively more mature OL lineage population,i.e.prooligodendroblast (pro-OL),than OPC,for transplantation after SCI.We found that pro-OLs responded to lipopolysaccharide (LPS)-stimulated microglia conditioned medium (L + M) by preserving toll-like receptor 4 (TLR4) expression,improving cell viability,and enhancing myelinating capability as compared to other OL lineage cells exposed to either LPS-stimulated or non-stimulated microglia conditioned medium (L-M).When stimulated pro-OLs were intrathecally delivered through a lumbar puncture after a T10 thoracic contusive SCI,they promoted behavior recovery assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale,stride length,and slips on the grid tests.Histologically,transplantation of stimulated pro-OLs caused a consid-erable increase in axon growth and myelination,and less accumulation of macrophages at the lesion site when compared to the vehicle control or OPC transplantation.Compared with direct transplantation of OPCs,inducing these cells to a more mature pro-OL stage and stimulating them with L + M may be more advantageous since the pro-OLs may have already ini-tiated the differentiation process towards OLs prior to transplantation.Thus,transplantation of pro-OLs,preconditioned by LPS-stimulated microglia conditioned medium,may offer a better therapeutic potential than OPCs for recovery after acute SCI.