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  • 1
    Online Resource
    Online Resource
    Neural Stem Cells: From Cell Biology to Cell Replacement
    SAGE Publications ; 2000
    In:  Cell Transplantation Vol. 9, No. 2 ( 2000-03), p. 139-152
    Details
    In: Cell Transplantation, SAGE Publications, Vol. 9, No. 2 ( 2000-03), p. 139-152
    Abstract: A large number of crippling neurological conditions result from the loss of certain cell populations from the nervous system through disease or injury, and these cells are not intrinsically replaced. Mounting evidence now suggests that replacement of depleted cell populations by transplantation may be of functional benefit in many such diseases. A diverse range of cell populations is vulnerable, and the loss of specific populations results in circumscribed deficits in different conditions. This diversity presents a considerable challenge if cell replacement therapy is to become widely applicable in the clinical domain, because each condition has specific requirements for the phenotype, developmental stage, and number of cells required. An ideal cell for universal application in cell replacement therapy would possess several key properties: it would be highly proliferative, allowing the ex vivo production of large numbers of cells from minimal donor material; it would also remain immature and phenotypically plastic such that it could differentiate into appropriate neural and glial cell types on, or prior to, transplantation. Critically, both proliferation and differentiation would be controllable. This review considers some of the evidence that stem cells exist in the central nervous system and that they may possess characteristics that make them ideal for broad application in cell replacement therapy.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    URL: Article
    DOI: 10.1177/096368970000900202
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2000
    detail.hit.zdb_id: 2020466-8
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  • 2
    Online Resource
    Online Resource
    Lesion-Induced Increase in Survival and Migration of Human Neural Progenitor Cells Releasing GDNF
    SAGE Publications ; 2008
    In:  Cell Transplantation Vol. 17, No. 7 ( 2008-07), p. 753-762
    Details
    In: Cell Transplantation, SAGE Publications, Vol. 17, No. 7 ( 2008-07), p. 753-762
    Abstract: The use of human neural progenitor cells (hNPC) has been proposed to provide neuronal replacement or astrocytes delivering growth factors for brain disorders such as Parkinson's and Huntington's disease. Success in such studies likely requires migration from the site of transplantation and integration into host tissue in the face of ongoing damage. In the current study, hNPC modified to release glial cell line-derived neurotrophic factor (hNPCGDNF) were transplanted into either intact or lesioned animals. GDNF release itself had no effect on the survival, migration, or differentiation of the cells. The most robust migration and survival was found using a direct lesion of striatum (Huntington's model) with indirect lesions of the dopamine system (Parkinson's model) or intact animals showing successively less migration and survival. No lesion affected differentiation patterns. We conclude that the type of brain injury dictates migration and integration of hNPC, which has important consequences when considering transplantation of these cells as a therapy for neurodegenerative diseases.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    URL: Article
    DOI: 10.3727/096368908786516819
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2008
    detail.hit.zdb_id: 2020466-8
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  • 3
    Online Resource
    Online Resource
    Emerging technologies and their impact on regulatory science
    SAGE Publications ; 2022
    In:  Experimental Biology and Medicine Vol. 247, No. 1 ( 2022-01), p. 1-75
    Details
    In: Experimental Biology and Medicine, SAGE Publications, Vol. 247, No. 1 ( 2022-01), p. 1-75
    Abstract: There is an evolution and increasing need for the utilization of emerging cellular, molecular and in silico technologies and novel approaches for safety assessment of food, drugs, and personal care products. Convergence of these emerging technologies is also enabling rapid advances and approaches that may impact regulatory decisions and approvals. Although the development of emerging technologies may allow rapid advances in regulatory decision making, there is concern that these new technologies have not been thoroughly evaluated to determine if they are ready for regulatory application, singularly or in combinations. The magnitude of these combined technical advances may outpace the ability to assess fit for purpose and to allow routine application of these new methods for regulatory purposes. There is a need to develop strategies to evaluate the new technologies to determine which ones are ready for regulatory use. The opportunity to apply these potentially faster, more accurate, and cost-effective approaches remains an important goal to facilitate their incorporation into regulatory use. However, without a clear strategy to evaluate emerging technologies rapidly and appropriately, the value of these efforts may go unrecognized or may take longer. It is important for the regulatory science field to keep up with the research in these technically advanced areas and to understand the science behind these new approaches. The regulatory field must understand the critical quality attributes of these novel approaches and learn from each other's experience so that workforces can be trained to prepare for emerging global regulatory challenges. Moreover, it is essential that the regulatory community must work with the technology developers to harness collective capabilities towards developing a strategy for evaluation of these new and novel assessment tools.
    Type of Medium: Online Resource
    ISSN: 1535-3702 , 1535-3699
    URL: Article
    DOI: 10.1177/15353702211052280
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2020856-X
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    GDNF-Secreting Human Neural Progenitor Cells Increase Tyrosine Hydroxylase and VMAT2 Expression in MPTP-Treated Cynomolgus Monkeys
    SAGE Publications ; 2008
    In:  Cell Transplantation Vol. 17, No. 4 ( 2008-04), p. 383-395
    Details
    In: Cell Transplantation, SAGE Publications, Vol. 17, No. 4 ( 2008-04), p. 383-395
    Abstract: Human neural progenitor cells (hNPCs) have been proposed as a potential source of cells for ex vivo gene therapy. In this pilot study, three 5-year-old female cynomolgus monkeys received a single intracarotid infusion of MPTP, followed 1 week later by MRI-guided stereotaxic intrastriatal and intranigral injections of male hNPCs transgenic for GDNF. Immunosupression with oral cyclosporine (30–40 mg/kg) began 48 h before hNPC transplants and continued throughout the study. We monitored the animals using a clinical rating scale (CRS). Three months postsurgery, we euthanized the animals by transcardiac perfusion, then retrieved and processed their brains for morphological analysis. Our findings include the following. 1) hNPCs survived and produced GDNF in all animals 3 months postsurgery. 2) hNPCs remained in the areas of injection as observed by GDNF immunostaining and in situ hybridization for the human Y chromosome. 3) A “halo” of GDNF expression was observed diffusing from the center of the graft out into the surrounding area. 4) We observed increased TH- and VMAT2-positive fibers in areas of GDNF delivery in two of the three animals. The two animals with TH- and VMAT2-positive fibers also showed reductions in their CRS scores. 5) Some GFAP-positive perivascular cuffing was found in transplanted areas. 6) General blood chemistry and necropsies did not reveal any abnormalities. Therefore, we conclude that hNPCs releasing GDNF may be a possible alternative for intracerebral trophic factor delivery in Parkinson's disease.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    URL: Article
    DOI: 10.3727/096368908784423300
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2008
    detail.hit.zdb_id: 2020466-8
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  • 5
    Online Resource
    Online Resource
    In Vivo Tracking of Human Neural Progenitor Cells in the Rat Brain Using Magnetic Resonance Imaging is Not Enhanced by Ferritin Expression
    SAGE Publications ; 2016
    In:  Cell Transplantation Vol. 25, No. 3 ( 2016-03), p. 575-592
    Details
    In: Cell Transplantation, SAGE Publications, Vol. 25, No. 3 ( 2016-03), p. 575-592
    Abstract: Rapid growth in the field of stem cell research has generated a lot of interest in their therapeutic use, especially in the treatment of neurodegenerative diseases. Specifically, human neural progenitor cells (hNPCs), unique in their capability to differentiate into cells of the neural lineage, have been widely investigated due to their ability to survive, thrive, and migrate toward injured tissues. Still, one of the major roadblocks for clinical applicability arises from the inability to monitor these cells following transplantation. Molecular imaging techniques, such as magnetic resonance imaging (MRI), have been explored to assess hNPC transplant location, migration, and survival. Here we investigated whether inducing hNPCs to overexpress ferritin (hNPCs Fer ), an iron storage protein, is sufficient to track these cells long term in the rat striatum using MRI. We found that increased hypointensity on MRI images could establish hNPC Fer location. Unexpectedly, however, wild-type hNPC transplants were detected in a similar manner, which is likely due to increased iron accumulation following transplantation-induced damage. Hence, we labeled hNPCs with superparamagnetic iron oxide (SPIO) nanoparticles to further increase iron content in an attempt to enhance cell contrast in MRI. SPIO-labeling of hNPCs (hNPCs-SPIO) achieved increased hypointensity, with significantly greater area of decreased T2* compared to hNPC Fer ( p 〈 0.0001) and all other controls used. However, none of the techniques could be used to determine graft rejection in vivo, which is imperative for understanding cell behavior following transplantation. We conclude that in order for cell survival to be monitored in preclinical and clinical settings, another molecular imaging technique must be employed, including perhaps multimodal imaging, which would utilize MRI along with another imaging modality.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    URL: Article
    DOI: 10.3727/096368915X688614
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
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  • 6
    Online Resource
    Online Resource
    Survival, Neuronal Differentiation, and Fiber Outgrowth of Propagated Human Neural Precursor Grafts in an Animal Model of Huntington's Disease
    SAGE Publications ; 2000
    In:  Cell Transplantation Vol. 9, No. 1 ( 2000-01), p. 55-64
    Details
    In: Cell Transplantation, SAGE Publications, Vol. 9, No. 1 ( 2000-01), p. 55-64
    Abstract: Expanded neural precursor cells provide an attractive alternative to primary fetal tissue for cell replacement therapies in neurodegenerative diseases. In this study we transplanted epigenetically propagated human neural precursor cells into a rat model of Huntington's disease. Neural precursors survived transplantation and large numbers differentiated to express neuronal antigens, including some that expressed DARPP-32, indicating a mature striatal phenotype had been adopted. Neuronal fibers from the grafts projected diffusely throughout the host brain, although there was no evidence that outgrowth was specifically target directed. This study supports the contention that propagated human neural precursors may ultimately be of use in therapeutic neural transplantation paradigms for diseases such as Huntington's disease.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    URL: Article
    DOI: 10.1177/096368970000900108
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2000
    detail.hit.zdb_id: 2020466-8
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