Induced pluripotent stem cells derived from human intervertebral disc cell for ameliorating neurologic dysfunctions after spinal cord injury

Abstract

Induced pluripotent stem cells (iPSCs) have emerged as a promising cell source for immune-compatible cell therapy. A variety of somatic cells, such as skin fibroblasts and blood cells, have been used to generate iPSCs. However, the most of spinal cord injury (SCI) is caused by spine fracture. During emergency surgery on SCI patients, this disc tissue is often removed as to-be-discarded “waste”. In this study, we generated iPSCs from human intervertebral disc cells obtained from patients with spinal cord injury during spine fusion surgery. We investigated the pluripotency of disc cell-derived iPSCs (diPSCs) and neural differentiation capability as well as therapeutic effect to evaluate whether disc cells are suitable as a material of patient-specific iPSC generation for the treatment of spinal cord injury.Through various analyzes, we confirmed that the diPSCs showed similar characteristics to human embryonic stem cells and were efficiently differentiated into neural progenitor cells (NPCs) with the capability of differentiation into mature neurons in vitro. To examine whether the transplantation of NPCs derived from diPSCs had therapeutic effects, NPCs were transplanted into mice 9 days after spinal cord injury. We detected a significant amelioration of hindlimb dysfunction during follow-up recovery periods. Histological analysis 5 weeks post-transplantation identified undifferentiated human NPCs (nestin+) as well as early (TUJ1+) and mature neurons (MAP2+) derived from NPCs. Furthermore, NPC transplantation demonstrated a preventive effect on spinal cord degeneration resulting from the secondary injury. In this study, we demonstrated that intervertebral discs removed during surgery, previously considered a “waste” tissue, are able to reuse for patient-specific iPSC gen eration, and showed the treatability of NPC derived from diPSCs in SCI model.