Induced pluripotent stem (iPS) cells are at the forefront of research in regenerative medicine and are envisaged as a source for personalized tissue repair and cell replacement therapy. Here, we demonstrate for the first time that oligodendrocyte progenitors (OPs) can be derived from iPS cells generated using either an episomal, non-integrating plasmid approach or standard integrating retroviruses that survive and differentiate into mature oligodendrocytes after early transplantation into the injured spinal cord. The efficiency of OP differentiation in all 3 lines tested ranged from 40% to 60% of total cells, comparable to those derived from human embryonic stem cells. iPS cell lines derived using episomal vectors or retroviruses generated a similar number of early neural progenitors and glial progenitors while the episomal plasmid-derived iPS line generated more OPs expressing late markers O1 and RIP. Moreover, we discovered that iPS-derived OPs (iPS-OPs) engrafted 24 hours following a moderate contusive spinal cord injury (SCI) in rats survived for approximately two months and that more than 70% of the transplanted cells differentiated into mature oligodendrocytes that expressed myelin associated proteins. Transplanted OPs resulted in a significant increase in the number of myelinated axons in animals that received a transplantation 24 h after injury. In addition, nearly a 5-fold reduction in cavity size and reduced glial scarring was seen in iPS-treated groups compared to the control group, which was injected with heat-killed iPS-OPs. Although further investigation is needed to understand the mechanisms involved, these results provide evidence that patient-specific, iPS-derived OPs can survive for three months and improve behavioral assessment (BBB) after acute transplantation into SCI. This is significant as determining the time in which stem cells are injected after SCI may influence their survival and differentiation capacity.

Objective Neuroprotection by hypothermia has been an important research topic over last two decades. In animal models of spinal cord injury (SCI), the primary focus has been assessing effects of hypothermia on behavioral and histological outcomes. While a few studies have investigated electrophysiological changes in descending motor pathways with motor evoked potentials recorded during cooling, we report here, hypothermia induced increased electrical conduction in the ascending spinal cord pathways with somatosensory evoked potentials (SSEPs) in injured rats. In our experiments these effects lasted long after the acute hypothermia and were accompanied with potential long term improvements in motor movement. Design Laboratory Investigation. Setting University Medical School. Subjects 21 Female Lewis Rats. Interventions Hypothermia. Measurements and Main Results All animals underwent spinal cord contusion, with the NYU-Impactor, by a 12.5mm weight drop at thoracic vertebra T8. A group (n=10) was randomly assigned for a systemic 2hr. hypothermia episode (32±0.5°C) initiated ~2.0hrs post-injury. 11 rats were controls with post-injury temperature maintained at 37±0.5°C for 2hrs. The two groups underwent pre-injury, weekly post-injury (up to 4wks) SSEP recordings and standard motor behavioral tests (BBB). Three randomly selected rats from each group were euthanized for histological analysis at post-injury Day 3 and Day 28. Compared to controls, the hypothermia group showed significantly higher SSEP amplitudes post-injury; with longer latencies. The BBB scores were also higher immediately after injury and 4 weeks later in the hypothermia group. Importantly, specific changes in the BBB scores in hypothermia group (not seen in controls) indicated regained functions critical for motor control. Histological evaluations showed more tissue preservation in hypothermia group. Conclusions Post-SCI, early systemic hypothermia provided significant neuroprotection weeks after injury via improved sensory electrophysiological signals in rats. This was accompanied by higher motor behavioral scores and more spared tissue in acute and post-acute periods after injury.