セミナー情報

Spinal cord injury is a major cause of paralysis. Currently, there are no effective therapies to reverse this disabling condition. Human embryonic stem cells (hESC) and induced pluripotent ste cells (ihPSC) hold great promise for the treatment of patients with many neurodegenerative diseases particularly those arising from cell loss or neural dysfunction including spinal cord injury (SCI). We evaluated the therapeutic effects of transplanted hESC-derived oligodendrocyte progenitors (OPC) and/or motoneuron progenitors (MP) on axonal remyelination and functional recovery of adult rats after complete spinal cord transection. OPC and/or MP were grafted into the site of injury in the acute phase. Based on Basso-Beattie-Bresnahan scores recovery of locomotor function was significantly enhanced in rats treated with OPC and/or MP when compared with control animals. When transplanted into the spinal cord immediately after complete transection OPC and MP survived, migrated and differentiated into mature oligodendrocytes and neurons showing in vivo electrophysiological activity. We analyzed the underlying mechanisms of functional recovery after cell transplantation and hypothesize that the regenerative signalling pathways activated in the host tissue by transplanted cells are crucial for the restoring locomotor ability. Here we showed that the transplantation of hESC-derived OPC and MP promote astrogliosis, through activation of Jagged1-dependent Notch and Jak/STAT signalling that support axonal survival.Taken together, these results indicate that OPC and MP derived from hESC could be a useful therapeutic strategy to repair injured spinal cord.