Human-induced pluripotent stem cells generated from intervertebral disc cells improve neurologic functions in spinal cord injury

Abstract

IntroductionInduced pluripotent stem cells (iPSCs) have emerged as a promising cell source for immune-compatible cell therapy. Although a variety of somatic cells have been tried for iPSC generation, it is still of great interest to test new cell types, especially those which are hardly obtainable in a normal situation.MethodsIn this study, we generated iPSCs by using the cells originated from intervertebral disc which were removed during a spinal operation after spinal cord injury. We investigated the pluripotency of disc cell-derived iPSCs (diPSCs) and neural differentiation capability as well as therapeutic effect in spinal cord injury.ResultsThe diPSCs displayed similar characteristics to human embryonic stem cells and were efficiently differentiated into neural precursor cells (NPCs) with the capability of differentiation into mature neurons in vitro.When the diPSC-derived 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 at 5 weeks after transplantation identified undifferentiated human NPCs (Nestin+) as well as early (Tuj1+) and mature (MAP2+) neurons derived from the transplanted NPCs. Furthermore, NPC transplantation demonstrated a preventive effect on spinal cord degeneration resulting from the secondary injury.ConclusionThis study revealed that intervertebral discs removed during surgery for spinal stabilization after spinal cord injury, previously considered a “waste” tissue, may provide a unique opportunity to study iPSCs derived from difficult-to-access somatic cells and a useful therapeutic resource for autologous cell replacement therapy in spinal cord injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0118-x) contains supplementary material, which is available to authorized users.

Stem cell transplantation and functional recovery after spinal cord injury: a systematic review and meta-analysis

“…Their capability to generate all kinds of cells provides an opportunity to replenish damaged and dysfunctional cells. In this regard, it seems that cell transplantation could be considered as a practical alternative for treating such injuries [ 6 7 8 ]. Actually, cell therapy can regenerate neural connections which in turn leads to improved functional recovery [ 9 ].…”

Progress in the Use of Induced Pluripotent Stem Cell-Derived Neural Cells for Traumatic Spinal Cord Injuries in Animal Populations: Meta-Analysis and Review

“…Out of a total of 22 reports that assessed iPSC‐derived neural cells for SCI treatment, the following studies were incorporated into the meta‐analysis . A few studies were excluded, because statistical significance could not be verified, motor recovery was not assessed, used a different scale to assess motor recovery, or focused on a cervical SCI model. Other studies were conducted in primates using iPSCs, and insufficient data were provided to perform a separate t ‐statistic.…”

Applications of induced pluripotent stem cell technologies in spinal cord injury

“…Nori (2011) Neuron-dominant differentiation, synaptic formation, angiogenesis, preservation of axons and myelination Fujimoto (2012) Neuron-dominant differentiation, synaptic formation, axonal preservation Kobayashi (2012) Neuron-dominant differentiation, angiogenesis, preservation of axons and myelination Nutt et al (2013) Tri-lineage differentiation Lu (2014) Neurite outgrowth and synaptic formation All (2015) Oligodendrocyte-dominant differentiation, reduction in cavity area, preserved spinal cord, myelination at EM study Li et al (2015) Astrocyte-dominant differentiation, reduction in lesion area, preserved diaphragm innervation and function Nori (2015) Transplantation of tumorigenic hiPSC-derived neural stem/progenitor cells Oh et al (2015) Intervertebral disc-derived hiPSCs, Differentiation into Nestin+ and neuronal cells, preserved tissue Pomeshchik et al (2015) Poor survival rate of grafts, no functional recovery Romanyuk et al (2015) Tri-lineage differentiation, tissue preservation, neuronal regeneration, up-regulation of trophic factors Kawabata (2016) Robust myelination, functional recovery Okubo (2016) Removing tumor-initiating cells by gamma-secretase inhibitor, neuron-dominant differentiation, tumor suppression TP: transplantation, f/u: follow up, NOD/SCID: non-obese diabetic/severe combined immunodeficient, ATN: athymic nude, hiPSC: human induced pluripotent stem cell, NPCs: neural precursor cells, NESCs: neuroepithelial-like stem cells, OPCs: oligodendrocyte progenitor cells; EM study: electron microscopic study. tumorigenicity, and immunogenicity related to cell transplantation .…”