Characterization and therapeutic evaluation of a Nestin+ CNP+ NG2+ cell population on mouse spinal cord injury

• Identification of Nestin+ CNP+ NG2+ subset from the embryonic rat cerebral cortex
• Nestin+ CNP+ NG2+ cells are distinct from OPCs.
• Nestin+ CNP+ NG2+ cells are novel multipotent progenitors.
• Cell transplantation promotes remyelination and neuronal regeneration after SCI.

The NG2 chondroitin sulfate proteoglycan-expressing neural cells (NG2 cells) have originally been considered as oligodendrocyte progenitor cells (OPCs). However, recent findings on their diverse functions and lineage heterogeneity demonstrated that the NG2 cells contain various sub-populations whose concrete features and therapeutic potential yet remained elucidated. In the present study, we characterized a Nestin+ 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP)+ NG2+ subpopulation from embryonic rat cerebral cortex. The Nestin+ CNP+ NG2+ cells exhibited remarkable progenitor characteristics. Having been immortalized by human telomerase reverse transcriptase (hTERT), the life span of Nestin+ CNP+ NG2+ cells was extended to 230 population doublings (PDs). With immortalized NG2 cells, we demonstrated their differentiation capacities to oligodendrocytes, astrocytes and neurons. Furthermore, transplanted into injured spinal cord of a mouse model, they were able to promote remyelination and neuronal regeneration, thereby enhancing the functional recovery. Our findings suggest that the Nestin+ CNP+ NG2+ progenitor cells could be a good alternative cell source of cell therapy for neurological disorders.