112 research outputs found

    Survival of syngeneic and allogeneic iPSC–derived neural precursors after spinal grafting in minipigs

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    The use of autologous (or syngeneic) cells derived from induced pluripotent stem cells (iPSCs) holds great promise for future clinical use in a wide range of diseases and injuries. It is expected that cell replacement therapies using autologous cells would forego the need for immunosuppression, otherwise required in allogeneic transplantations. However, recent studies have shown the unexpected immune rejection of undifferentiated autologous mouse iPSCs after transplantation. Whether similar immunogenic properties are maintained in iPSC-derived lineage-committed cells (such as neural precursors) is relatively unknown. We demonstrate that syngeneic porcine iPSC-derived neural precursor cell (NPC) transplantation to the spinal cord in the absence of immunosuppression is associated with long-term survival and neuronal and glial differentiation. No tumor formation was noted. Similar cell engraftment and differentiation were shown in spinally injured transiently immunosuppressed swine leukocyte antigen (SLA)–mismatched allogeneic pigs. These data demonstrate that iPSC-NPCs can be grafted into syngeneic recipients in the absence of immunosuppression and that temporary immunosuppression is sufficient to induce long-term immune tolerance after NPC engraftment into spinally injured allogeneic recipients. Collectively, our results show that iPSC-NPCs represent an alternative source of transplantable NPCs for the treatment of a variety of disorders affecting the spinal cord, including trauma, ischemia, or amyotrophic lateral sclerosis

    Effect of plasma shaping on performance in the National Spherical Torus Experiment

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    The National Spherical Torus Experiment (NSTX) has explored the effects of shaping on plasma performance as determined by many diverse topics including the stability of global magnetohydrodynamic (MHD) modes (e.g., ideal external kinks and resistive wall modes), edge localized modes (ELMs), bootstrap current drive, divertor flux expansion, and heat transport. Improved shaping capability has been crucial to achieving Ξ’t ∼40%. Precise plasma shape control has been achieved on NSTX using real-time equilibrium reconstruction. NSTX has simultaneously achieved elongation κ∼2.8 and triangularity δ∼0.8. Ideal MHD theory predicts increased stability at high values of shaping factor S≑ q95 Ip (a Bt), which has been observed at large values of the S∼37 [MA (mΒ·T)] on NSTX. The behavior of ELMs is observed to depend on plasma shape. A description of the ELM regimes attained as shape is varied will be presented. Increased shaping is predicted to increase the bootstrap fraction at fixed Ip. The achievement of strong shaping has enabled operation with 1 s pulses with Ip =1 MA, and for 1.6 s for Ip =700 kA. Analysis of the noninductive current fraction as well as empirical analysis of the achievable plasma pulse length as elongation is varied will be presented. Data are presented showing a reduction in peak divertor heat load due to increasing in flux expansion. Β© 2006 American Institute of Physics

    Transcriptional Signature and Memory Retention of Human-Induced Pluripotent Stem Cells

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    Genetic reprogramming of somatic cells to a pluripotent state (induced pluripotent stem cells or iPSCs) by over-expression of specific genes has been accomplished using mouse and human cells. However, it is still unclear how similar human iPSCs are to human Embryonic Stem Cells (hESCs). Here, we describe the transcriptional profile of human iPSCs generated without viral vectors or genomic insertions, revealing that these cells are in general similar to hESCs but with significant differences. For the generation of human iPSCs without viral vectors or genomic insertions, pluripotent factors Oct4 and Nanog were cloned in episomal vectors and transfected into human fetal neural progenitor cells. The transient expression of these two factors, or from Oct4 alone, resulted in efficient generation of human iPSCs. The reprogramming strategy described here revealed a potential transcriptional signature for human iPSCs yet retaining the gene expression of donor cells in human reprogrammed cells free of viral and transgene interference. Moreover, the episomal reprogramming strategy represents a safe way to generate human iPSCs for clinical purposes and basic research

    Status and Plans for the National Spherical Torus Experimental Research Facility

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    Human Neural Stem Cells Differentiate and Promote Locomotor Recovery in an Early Chronic Spinal coRd Injury NOD-scid Mouse Model

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    Traumatic spinal cord injury (SCI) results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns) were prospectively isolated based on fluorescence-activated cell sorting for a CD133(+) and CD24(-/lo) population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery.hCNS-SCns were transplanted into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury. hCNS-SCns transplanted mice demonstrated significantly improved locomotor recovery compared to vehicle controls using open field locomotor testing and CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns integrated with the host as demonstrated by co-localization of human cytoplasm with discrete staining for the paranodal marker contactin-associated protein.The results suggest that hCNS-SCns are capable of surviving, differentiating, and promoting improved locomotor recovery when transplanted into an early chronic injury microenvironment. These data suggest that hCNS-SCns transplantation has efficacy in an early chronic SCI setting and thus expands the "window of opportunity" for intervention

    Review of deuterium–tritium results from the Tokamak Fusion Test Reactor

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    Overview of recent physics results from the National Spherical Torus Experiment (NSTX)

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