Cell therapy for spinal cord injury using induced pluripotent stem cells

Abstract

For the past few decades, spinal cord injury (SCI) has been believed to be an incurable traumatic condition, but with recent developments in stem cell biology, the field of regenerative medicine has gained hopeful momentum in the development of a treatment for this challenging pathology. Among the treatment candidates, transplantation of neural precursor cells has gained remarkable attention as a reasonable therapeutic intervention to replace the damaged central nervous system cells and promote functional recovery. Here, we highlight transplantation therapy techniques using induced pluripotent stem cells to treat SCI and review the recent research giving consideration to future clinical applications.

Keywords: ASIA, American Spinal Injury Association; C-ABC, chondroitinase ABC; CSPGs, chondroitin sulfate proteoglycans; CST, corticospinal tract; CiRA, the Center for iPS Cell Research and Application; Clinical application; ESCs, embryonic stem cells; GCV, ganciclovir; GSI, γ-secretase inhibitor; HLA, human leukocyte antigen; HMGB1, high mobility group box-1; HSVtk, herpes simplex virus type I thymidine kinase; Induced pluripotent stem cells; MLR, mixed lymphocyte reaction; NHPs, nonhuman primates; NPCs, neural precursor cells; Neural precursor cells; OPCs, oligodendrocyte progenitor cells; PBMCs, peripheral blood mononuclear cells; SCI, spinal cord injury; SLA, swine leukocyte antigen; Spinal cord injury; drNPCs, directly reprogrammed neural precursor cells; iPSCs, induced pluripotent stem cells.

Fig. 1

Roles of transplanted neural precursor cells in spinal cord injury. There are three mechanisms for tissue recovery after cell transplantation. (A) The grafted cells differentiate into neurons and form synapses with host neuronal cells. (B) The transplanted cells differentiate into oligodendrocytes and myelinated host axons. (C) The grafts secrete neurotrophic factors and prevent secondary damage.

Fig. 2

Strategy to prevent tumorigenicity after transplantation. (A) A γ-secretase inhibitor (GSI) promotes maturation and neuronal differentiation of neural precursor cells (NPCs). As a result, tumor-initiating cells are removed before transplantation. (B) Thorough investigation is important for the iPSCs and the derivative NPCs prior to transplantation. Only safe and effective cells after a proper quality check should be transplanted. (C) The NPCs are pushed to become more mature oligodendrocyte progenitor cells (OPCs) before transplantation. (D) Suicide genes are integrated into NPCs beforehand. If transplanted cells show tumorigenicity, an apoptosis inducer should be injected systematically.