Regenerative medicine for spinal cord injury using olfactory mucosa autografts

Abstract

The central nervous system has limited regenerative capacity, and functional restoration of the damaged system is difficult. Treatment is still limited to cerebrospinal protection after injury and reconstruction of neural networks by rehabilitation. In case of incomplete spinal cord injury, neural networks can be reconstructed because nerve tissues remain at the site of the injury. However, in case of complete spinal cord injury, all scaffolds for reconstruction of neural networks are lost. Thus, functional recovery through rehabilitation cannot be expected. At present, enhancement of residual function is the only treatment approach. Regarding spinal cord injury, expectations have been placed on regenerative medicine using stem cells including induced pluripotent stem cells, which have recently captured attention. However, regenerative medicine using stem cells is effective only during the acute-To-subacute phase, a period before scar tissues are formed in the injured spinal cord. Regenerative medicine using stem cells is completely ineffective in the chronic phase. In case of planning treatment for chronic-phase spinal cord injury, it is necessary to supply scaffolds where neuronal axons can grow to form neural networks, neurons, and neurotrophic factors for growth and protection of neuronal axons. In other words, all of the three elements, i.e., scaffolds, neurons, and neurotrophic factors are necessary. In addition, transplantation including these three elements requires avoiding ethical problems and immunological rejection. These conditions are not satisfied by cell transplantation, but by tissue transplantation, particularly by autologous tissue transplantation. The olfactory mucosa contains olfactory nerves associated with olfaction and is an extracranial region with exceptionally active nerve regeneration. The mucosa, which is embryologically derived from the central nerve as primordium, contains stem cells, olfactory ensheathing cells that have axonal growth effects, and various neurotrophic factors. The mucosa is endoscopically resectable and spontaneously regenerates after resection. Because the olfactory mucosa allows active nerve regeneration under physiological conditions, it is considered useful as a scaffold for neuronal axon regeneration. We conducted an animal study and then a human clinical study on treatment of chronic spinal cord injury using olfactory mucosa autografts. At the end of 2011, this treatment was designated as an advanced medical treatment.