Regenerative therapy for spinal cord injury using iPSC technology

Spinal cord injury (SCI) is a devastating event that causes permanent neurologic impairments. Cell transplantation therapy using neural precursor cells (NPCs) is a promising intervention aiming to replace damaged neural tissue and restore certain functions. Our group reported beneficial effects of iPSC-derived NPC transplantation and addressed safety issues on tumorigenicity after grafting. These findings will soon be tested at the clinical trial stage, the protocol of which has already been approved by the Ministry of Health, Labour and Welfare in Japan. We recently demonstrated the modest efficacy of gamma secretase inhibitor treatment of iPSC-NPCs before transplantation at the chronic phase. However, more comprehensive strategies involving combinatory therapies are essential to enhance current spinal cord regeneration treatments.

• 1
  Grafted NPCs differentiated into three neural lineages without tumor formation. The differentiated oligodendrocytes enhanced remyelination for host neuronal axons and induced neurite regrowth of 5-HT+ serotonergic fibers around the lesion area, which led to locomotor functional recovery.
• 2
  Transplanted cells predominantly differentiated into neurons without tumorigenicity, promoted axonal regrowth, and preserved entire host tissues, including the myelination region. These positive effects resulted in functional recovery in the animals receiving NPCs.
• 3
  Pre-treatment with GSI can eliminate tumor-initiating cells in human iPSC-NPCs or promote differentiation of the cells into mature neuronal cells. These beneficial mechanisms potentially mitigated the safety issue related to tumorigenicity after cell transplantation.