Purpose of review To describe the current status of testing Schwann cell transplantation as a therapy for human spinal cord injury (SCI). Recent findings Transplanted Schwann cells have reparative effects in the damaged spinal cord. A few clinical studies have reported that Schwann cell transplantation appears safe. Compared with allogeneic cell transplants, autologous cells do not require immune suppression, but the workload of cell manufacturing is greater. Preclinical Schwann cell transplant studies conducted at the University of Miami in 2009–2012 supported an investigational new drug approved by the Food and Drug Administration. A Phase 1 safety study has been initiated. Summary Spinal cord repair after severe SCI requires that axonal regeneration and myelination occur in a context of reduced inhibition, enhanced plasticity, and new circuit formation. Evolving clinical experience with Schwann cell transplantation may provide a basis upon which additionally combined therapeutics can be tested to increase the extent of repair after SCI. Safety is the primary consideration when ex-vivo manipulated cells are introduced into the damaged nervous system. Preclinical studies across several species have not indicated safety concerns regarding Schwann cells. Initial clinical reports from studies in Iran and China are suggestive of clinical safety, although more rigorous characterization of the implanted cells is needed.

The histological assessment of spinal cord tissue in three dimensions has previously been very time consuming and prone to errors of interpretation. Advances in tissue clearing have significantly improved visualization of fluorescently labelled axons. While recent proof-of-concept studies have been performed with transgenic mice in which axons were prelabeled with GFP, investigating axonal regeneration requires stringent axonal tracing methods as well as the use of animal models in which transgenic axonal labeling is not available. Using rodent models of spinal cord injury, we labeled axon tracts of interest using both adeno-associated virus and chemical tracers and performed tetrahydrofuran-based tissue clearing to image multiple axon types in spinal cords using light sheet and confocal microscopy. Using this approach, we investigated the relationships between axons and scar-forming cells at the injury site as well as connections between sensory axons and motor pools in the spinal cord. In addition, we used these methods to trace axons in nonhuman primates. This reproducible and adaptable virus-based approach can be combined with transgenic mice or with chemical-based tract-tracing methods, providing scientists with flexibility in obtaining axonal trajectory information from transparent tissue.

PURPOSE: To evaluate the effect of various implant-level impression techniques on the accuracy of definitive casts for a multiple internal connection implant system with different implant angulations and subgingival depths. MATERIAL AND METHODS: Six tapered Screw-Vent implants were placed in a reference model with different angles (0, 15, and 30 degrees) and subgingival positions (0, 1, and 3 mm). Twenty medium-consistency polyether impressions of this model were made with 4 techniques (n = 5 per group): (1) indirect technique, (2) unsplinted direct technique, (3) acrylic resin-splinted direct technique, and (4) metal-splinted direct technique. Impressions were poured with type IV dental stone. The interimplant distances were measured for casts using a coordinate measuring machine and the deviations compared with the reference model were calculated. Data were analyzed using intraclass correlation coefficient, ANOVA and Bonferroni test ( = 0.05). RESULTS: Four impression procedures showed significant differences (P = 0.0001). Only group 4 casts showed no significant differences in comparison with the reference model (P = 0.666) (ANOVA repeated measures). CONCLUSIONS: The impression procedure affected the accuracy of definitive casts. The metal-splinted direct technique produced the most accurate casts, followed by acrylic resin-splinted direct, indirect, and unsplinted direct techniques. ABSTRACT (199 words)Purpose To evaluate the effect of four implant-level impression techniques on the accuracy of

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Background: Deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) has been studied as a therapeutic target in rodent models of stroke, parkinsonism, and spinal cord injury. Clinical DBS trials have targeted the closely related pedunculopontine nucleus in patients with Parkinson's disease as a therapy for gait dysfunction, with mixed reported outcomes. Recent studies suggest that optimizing the MLR target could improve its effectiveness. Objective: We sought to determine if stereotaxic targeting and DBS in the midbrain of the pig, in a region anatomically similar to that previously identified as the MLR in other species, could initiate and modulate ongoing locomotion, as a step towards generating a large animal neuromodulation model of gait. Methods: We implanted Medtronic 3389 electrodes into putative MLR structures in Yucatan micropigs to characterize the locomotor effects of acute DBS in this region, using EMG recordings, joint kinematics, and speed measurements on a manual treadmill. Results: MLR DBS initiated and augmented locomotion in freely moving micropigs. Effective locomotor sites centered around the cuneiform nucleus and stimulation frequency controlled locomotor speed and stepping frequency. Off-target stimulation evoked defensive and aversive behaviors that precluded locomotion in the animals. Conclusion: Pigs appear to have an MLR and can be used to model neuromodulation of this gaitpromoting center. These results indicate that the pig is a useful model to guide future clinical studies for optimizing MLR DBS in cases of gait deficiencies associated with such conditions as Parkinson's disease, spinal cord injury, or stroke.

SummaryHigher susceptibility of newborns to infections has been attributed to the hypo-responsiveness of their cellular immune system. Here we compared the activation status and expression of cytokines and cytotoxic molecules of cord versus maternal peripheral blood mononuclear cells in an African population. Human leucocyte antigen-DR was expressed on a lower percentage of cord compared to maternal cd and CD3 + T cells. Similarly, a lower proportion of cord versus maternal cd and CD3 + T cells displayed perforin, granzyme B and cytokine activity either ex vivo or following non-specific stimulation in vitro. In contrast, comparable proportions of cord and maternal CD94 + CD3 -natural killer (NK) cells showed perforin and granzyme B expression ex vivo. We conclude that cord blood cd and CD3 + T cells are functionally hypo-responsive as reflected by reduced numbers of such cells expressing either an activation marker, T helper 1 (Th1) and Th2 cytokines or cytotoxic effector molecules. The similarity in numbers of cord and maternal CD94 + CD3 -cells expressing cytotoxic effector molecules suggests that neonatal Africans' NK cells may be functionally mature.