The Experts below are selected from a list of 4368 Experts worldwide ranked by ideXlab platform
Jerrod Denham - One of the best experts on this subject based on the ideXlab platform.
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human embryonic stem cell derived Oligodendrocyte Progenitor cells preclinical efficacy and safety in cervical spinal cord injury
Stem Cells Translational Medicine, 2017Co-Authors: Nathan C Manley, Jerrod Denham, Catherine Priest, Edward D Wirth, Jane S LebkowskiAbstract:Cervical spinal cord injury (SCI) remains an important research focus for regenerative medicine given the potential for severe functional deficits and the current lack of treatment options to augment neurological recovery. We recently reported the preclinical safety data of a human embryonic cell-derived Oligodendrocyte Progenitor cell (OPC) therapy that supported initiation of a phase I clinical trial for patients with sensorimotor complete thoracic SCI. To support the clinical use of this OPC therapy for cervical injuries, we conducted preclinical efficacy and safety testing of the OPCs in a nude rat model of cervical SCI. Using the automated TreadScan system to track motor behavioral recovery, we found that OPCs significantly improved locomotor performance when administered directly into the cervical spinal cord 1 week after injury, and that this functional improvement was associated with reduced parenchymal cavitation and increased sparing of myelinated axons within the injury site. Based on large scale biodistribution and toxicology studies, we show that OPC migration is limited to the spinal cord and brainstem and did not cause any adverse clinical observations, toxicities, allodynia, or tumors. In combination with previously published efficacy and safety data, the results presented here supported initiation of a phase I/IIa clinical trial in the U.S. for patients with sensorimotor complete cervical SCI. Stem Cells Translational Medicine 2017;6:1917-1929.
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immunological properties of human embryonic stem cell derived Oligodendrocyte Progenitor cells
Journal of Neuroimmunology, 2007Co-Authors: Ross M Okamura, Jane S Lebkowski, Catherine Priest, Jerrod Denham, Anish Sen MajumdarAbstract:A major concern in the use of allotransplantation of human embryonic stem cell (hESC)-based therapies is the possibility of allogeneic rejection by the host's immune system. In this report, we determined the immunological properties of hESC-derived Oligodendrocyte Progenitor cells (OPC) that have the potential for clinical application for the treatment of patients with spinal cord injury. In vitro immunological studies suggest that hESC-derived OPCs are poor targets for both the innate and the adaptive human immune effector cells as well as resistant to lysis by anti-Neu5Gc antibodies. These results indicate that hESC-derived OPCs retain some of the unique immunological properties of the parental cell line from which they were differentiated.
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Oligodendrocyte Progenitor cells derived from human embryonic stem cells express neurotrophic factors
Stem Cells and Development, 2006Co-Authors: Yi Wei Zhang, Jerrod Denham, Scott R ThiesAbstract:Oligodendrocyte Progenitor cells (OPCs) derived from human embryonic stem (hES) cells have been reported to remyelinate axons and improve locomotor function in a rodent model of spinal cord injury. Although remyelination would be expected to have a beneficial effect in spinal cord injury, neurotrophic factor expression may also contribute to functional recovery. Neurotrophic factors could impact the survival of axotomized neurons, as well as promote axonal regeneration in interrupted conduction pathways. This study demonstrates that hES cell-derived OPCs express functional levels of midkine, hepatocyte growth factor (HGF), activin A, transforming growth factor-β2 (TGF-β2), and brain-derived neurotrophic factor (BDNF), proteins with reported trophic effects on neurons. The neurotrophic activity of hES cell-derived OPCs is further demonstrated by stimulatory effects on neurite outgrowth of adult rat sensory neurons in vitro.
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Oligodendrocyte Progenitor cells derived from human embryonic stem cells express neurotrophic factors
Stem Cells and Development, 2006Co-Authors: Yi Wei Zhang, Jerrod Denham, Scott R ThiesAbstract:Oligodendrocyte Progenitor cells (OPCs) derived from human embryonic stem (hES) cells have been reported to remyelinate axons and improve locomotor function in a rodent model of spinal cord injury. Although remyelination would be expected to have a beneficial effect in spinal cord injury, neurotrophic factor expression may also contribute to functional recovery. Neurotrophic factors could impact the survival of axotomized neurons, as well as promote axonal regeneration in interrupted conduction pathways. This study demonstrates that hES cell-derived OPCs express functional levels of midkine, hepatocyte growth factor (HGF), activin A, transforming growth factor-beta2 (TGF-beta2), and brain-derived neurotrophic factor (BDNF), proteins with reported trophic effects on neurons. The neurotrophic activity of hES cell-derived OPCs is further demonstrated by stimulatory effects on neurite outgrowth of adult rat sensory neurons in vitro.
Hans S. Keirstead - One of the best experts on this subject based on the ideXlab platform.
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human embryonic stem cell derived Oligodendrocyte Progenitor cell transplants improve recovery after cervical spinal cord injury
Stem Cells, 2009Co-Authors: Jason Sharp, Gabriel Nistor, Jennifer Frame, Monica M Siegenthaler, Hans S. KeirsteadAbstract:Evidence that cell transplants can improve recovery outcomes in spinal cord injury (SCI) models substantiates treatment strategies involving cell replacement for humans with SCI. Most pre-clinical studies of cell replacement in SCI examine thoracic injury models. However, as most human injuries occur at the cervical level, it is critical to assess potential treatments in cervical injury models and examine their effectiveness using at-level histological and functional measures. To directly address cervical SCI, we used a C5 midline contusion injury model and assessed the efficacy of a candidate therapeutic for thoracic SCI in this cervical model. The contusion generates reproducible, bilateral movement and histological deficits, although a number of injury parameters such as acute severity of injury, affected gray-to-white matter ratio, extent of endogenous remyelination, and at-level locomotion deficits do not correspond with these parameters in thoracic SCI. On the basis of reported benefits in thoracic SCI, we transplanted human embryonic stem cell (hESC)-derived Oligodendrocyte Progenitor cells (OPCs) into this cervical model. hESC-derived OPC transplants attenuated lesion pathogenesis and improved recovery of forelimb function. Histological effects of transplantation included robust white and gray matter sparing at the injury epicenter and, in particular, preservation of motor neurons that correlated with movement recovery. These findings further our understanding of the histopathology and functional outcomes of cervical SCI, define potential therapeutic targets, and support the use of these cells as a treatment for cervical SCI. STEM CELLS 2010;28:152–163
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human embryonic stem cell derived Oligodendrocyte Progenitor cell transplants improve recovery after cervical spinal cord injury
Stem Cells, 2009Co-Authors: Jason Sharp, Gabriel Nistor, Jennifer Frame, Monica M Siegenthaler, Hans S. KeirsteadAbstract:Evidence that cell transplants can improve recovery outcomes in spinal cord injury (SCI) models substantiates treatment strategies involving cell replacement for humans with SCI. Most pre-clinical studies of cell replacement in SCI examine thoracic injury models. However, as most human injuries occur at the cervical level, it is critical to assess potential treatments in cervical injury models and examine their effectiveness using at-level histological and functional measures. To directly address cervical SCI, we used a C5 midline contusion injury model and assessed the efficacy of a candidate therapeutic for thoracic SCI in this cervical model. The contusion generates reproducible, bilateral movement and histological deficits, although a number of injury parameters such as acute severity of injury, affected gray-to-white matter ratio, extent of endogenous remyelination, and at-level locomotion deficits do not correspond with these parameters in thoracic SCI. On the basis of reported benefits in thoracic SCI, we transplanted human embryonic stem cell (hESC)-derived Oligodendrocyte Progenitor cells (OPCs) into this cervical model. hESC-derived OPC transplants attenuated lesion pathogenesis and improved recovery of forelimb function. Histological effects of transplantation included robust white and gray matter sparing at the injury epicenter and, in particular, preservation of motor neurons that correlated with movement recovery. These findings further our understanding of the histopathology and functional outcomes of cervical SCI, define potential therapeutic targets, and support the use of these cells as a treatment for cervical SCI.
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human embryonic stem cell derived Oligodendrocyte Progenitor cell transplants remyelinate and restore locomotion after spinal cord injury
The Journal of Neuroscience, 2005Co-Authors: Hans S. Keirstead, Gabriel Nistor, Giovanna M Bernal, Minodora O Totoiu, Frank Cloutier, Kelly Sharp, Oswald StewardAbstract:Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived Oligodendrocyte Progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into Oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.
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response of the Oligodendrocyte Progenitor cell population defined by ng2 labelling to demyelination of the adult spinal cord
Glia, 1998Co-Authors: Hans S. Keirstead, Joel M Levine, W F BlakemoreAbstract:Elucidation of the response of Oligodendrocyte Progenitor cell populations to demyelination in the adult central nervous system (CNS) is critical to understanding why remyelination fails in multiple sclerosis. Using the anti-NG2 monoclonal antibody to identify Oligodendrocyte Progenitor cells, we have documented their response to antibody-induced demyelination in the dorsal column of the adult rat spinal cord. The number of NG2+ cells in the vicinity of demyelinated lesions increased by 72% over the course of 3 days following the onset of demyelination. This increase in NG2+ cell numbers did not reflect a nonspecific staining of reactive cells, as GFAP, OX-42, and Rip antibodies did not co-localise with NG2 + cells in double immunostained tissue sections. NG2 + cells incorporated BrdU 48-72 h following the onset of demyelination. After the onset of remyelination (10-14 days), the number of NG2+ cells decreased to 46% of control levels and remained consistently low for 2 months. When spinal cords were exposed to 40 Grays of x-irradiation prior to demyelination, the number of NG2+ cells decreased to 48% of control levels by 3 days following the onset of demyelination and remained unchanged at 3 weeks. Since 40 Grays of x-irradiation kills dividing cells, these studies illustrate a responsive and nonresponsive NG2+ cell population following demyelination in the adult spinal cord and suggest that the responsive NG2+ cell population does not renew itself.
Scott R Thies - One of the best experts on this subject based on the ideXlab platform.
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Oligodendrocyte Progenitor cells derived from human embryonic stem cells express neurotrophic factors
Stem Cells and Development, 2006Co-Authors: Yi Wei Zhang, Jerrod Denham, Scott R ThiesAbstract:Oligodendrocyte Progenitor cells (OPCs) derived from human embryonic stem (hES) cells have been reported to remyelinate axons and improve locomotor function in a rodent model of spinal cord injury. Although remyelination would be expected to have a beneficial effect in spinal cord injury, neurotrophic factor expression may also contribute to functional recovery. Neurotrophic factors could impact the survival of axotomized neurons, as well as promote axonal regeneration in interrupted conduction pathways. This study demonstrates that hES cell-derived OPCs express functional levels of midkine, hepatocyte growth factor (HGF), activin A, transforming growth factor-β2 (TGF-β2), and brain-derived neurotrophic factor (BDNF), proteins with reported trophic effects on neurons. The neurotrophic activity of hES cell-derived OPCs is further demonstrated by stimulatory effects on neurite outgrowth of adult rat sensory neurons in vitro.
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Oligodendrocyte Progenitor cells derived from human embryonic stem cells express neurotrophic factors
Stem Cells and Development, 2006Co-Authors: Yi Wei Zhang, Jerrod Denham, Scott R ThiesAbstract:Oligodendrocyte Progenitor cells (OPCs) derived from human embryonic stem (hES) cells have been reported to remyelinate axons and improve locomotor function in a rodent model of spinal cord injury. Although remyelination would be expected to have a beneficial effect in spinal cord injury, neurotrophic factor expression may also contribute to functional recovery. Neurotrophic factors could impact the survival of axotomized neurons, as well as promote axonal regeneration in interrupted conduction pathways. This study demonstrates that hES cell-derived OPCs express functional levels of midkine, hepatocyte growth factor (HGF), activin A, transforming growth factor-beta2 (TGF-beta2), and brain-derived neurotrophic factor (BDNF), proteins with reported trophic effects on neurons. The neurotrophic activity of hES cell-derived OPCs is further demonstrated by stimulatory effects on neurite outgrowth of adult rat sensory neurons in vitro.
Jane S Lebkowski - One of the best experts on this subject based on the ideXlab platform.
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safety of direct injection of Oligodendrocyte Progenitor cells into the spinal cord of uninjured gottingen minipigs
Journal of Neurosurgery, 2021Co-Authors: Richard G Fessler, Jane S Lebkowski, Charles Y Liu, Stephen Mckenna, David R Fessler, Catherine A Priest, Edward D WirthAbstract:Objective This study was conducted as a final proof-of-safety direct injection of Oligodendrocyte Progenitor cells into the uninjured spinal cord prior to translation to the human clinical trials. Methods In this study, 107 Oligodendrocyte Progenitor cells (LCTOPC1, also known as AST-OPC1 and GRNOPC1) in 50-μL suspension were injected directly into the uninjured spinal cords of 8 immunosuppressed Gottingen minipigs using a specially designed stereotactic delivery device. Four additional Gottingen minipigs were given Hanks' Balanced Salt Solution and acted as the control group. Results Cell survival and no evidence of histological damage, abnormal inflammation, microbiological or immunological abnormalities, tumor formation, or unexpected morbidity or mortality were demonstrated. Conclusions These data strongly support the safety of intraparenchymal injection of LCTOPC1 into the spinal cord using a model anatomically similar to that of the human spinal cord. Furthermore, this research provides guidance for future clinical interventions, including mechanisms for precise positioning and anticipated volumes of biological payloads that can be safely delivered directly into uninjured portions of the spinal cord.
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human embryonic stem cell derived Oligodendrocyte Progenitor cells preclinical efficacy and safety in cervical spinal cord injury
Stem Cells Translational Medicine, 2017Co-Authors: Nathan C Manley, Jerrod Denham, Catherine Priest, Edward D Wirth, Jane S LebkowskiAbstract:Cervical spinal cord injury (SCI) remains an important research focus for regenerative medicine given the potential for severe functional deficits and the current lack of treatment options to augment neurological recovery. We recently reported the preclinical safety data of a human embryonic cell-derived Oligodendrocyte Progenitor cell (OPC) therapy that supported initiation of a phase I clinical trial for patients with sensorimotor complete thoracic SCI. To support the clinical use of this OPC therapy for cervical injuries, we conducted preclinical efficacy and safety testing of the OPCs in a nude rat model of cervical SCI. Using the automated TreadScan system to track motor behavioral recovery, we found that OPCs significantly improved locomotor performance when administered directly into the cervical spinal cord 1 week after injury, and that this functional improvement was associated with reduced parenchymal cavitation and increased sparing of myelinated axons within the injury site. Based on large scale biodistribution and toxicology studies, we show that OPC migration is limited to the spinal cord and brainstem and did not cause any adverse clinical observations, toxicities, allodynia, or tumors. In combination with previously published efficacy and safety data, the results presented here supported initiation of a phase I/IIa clinical trial in the U.S. for patients with sensorimotor complete cervical SCI. Stem Cells Translational Medicine 2017;6:1917-1929.
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immunological properties of human embryonic stem cell derived Oligodendrocyte Progenitor cells
Journal of Neuroimmunology, 2007Co-Authors: Ross M Okamura, Jane S Lebkowski, Catherine Priest, Jerrod Denham, Anish Sen MajumdarAbstract:A major concern in the use of allotransplantation of human embryonic stem cell (hESC)-based therapies is the possibility of allogeneic rejection by the host's immune system. In this report, we determined the immunological properties of hESC-derived Oligodendrocyte Progenitor cells (OPC) that have the potential for clinical application for the treatment of patients with spinal cord injury. In vitro immunological studies suggest that hESC-derived OPCs are poor targets for both the innate and the adaptive human immune effector cells as well as resistant to lysis by anti-Neu5Gc antibodies. These results indicate that hESC-derived OPCs retain some of the unique immunological properties of the parental cell line from which they were differentiated.
Jing Bian - One of the best experts on this subject based on the ideXlab platform.
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rapid and efficient differentiation of rodent neural stem cells into Oligodendrocyte Progenitor cells
Developmental Neuroscience, 2019Co-Authors: Jiao Zheng, Linlin Chai, Mengsi Lin, Ruocheng Zeng, Jing BianAbstract:Oligodendrocyte Progenitor cells (OPCs) may have beneficial effects in cell replacement therapy of neurodegenerative disease owing to their unique capability to differentiate into myelinogenic Oligodendrocytes (OLs) in response to extrinsic signals. Therefore, it is of significance to establish an effective differentiation methodology to generate highly pure OPCs and OLs from some easily accessible stem cell sources. To achieve this goal, in this study, we present a rapid and efficient protocol for oligodendroglial lineage differentiation from mouse neural stem cells (NSCs), rat NSCs, or mouse embryonic stem cell-derived neuroepithelial stem cells. In a defined culture medium containing Smoothened Agonist, basic fibroblast growth factor, and platelet-derived growth factor-AA, OPCs could be generated from the above stem cells over a time course of 4-6 days, achieving a cell purity as high as ∼90%. In particular, these derived OPCs showed high expandability and could further differentiate into myelin basic protein-positive OLs within 3 days or alternatively into glial fibrillary acidic protein-positive astrocytes within 7 days. Furthermore, transplantation of rodent NSC-derived OPCs into injured spinal cord indicated that it is a feasible strategy to treat spinal cord injury. Our results suggest a differentiation strategy for robust production of OPCs and OLs from rodent stem cells, which could provide an abundant OPC source for spinal cord injury.
