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Kwang-hyun Baek - One of the best experts on this subject based on the ideXlab platform.

  • Cellular functions of stem cell factors mediated by the ubiquitin–proteasome system
    Cellular and Molecular Life Sciences, 2018
    Co-Authors: Jihye Choi, Kwang-hyun Baek
    Abstract:

    Stem cells undergo partitioning through mitosis and separate into specific cells of each of the three embryonic germ layers: endoderm, mesoderm, and ectoderm. Pluripotency, reprogramming, and self-renewal are essential elements of embryonic stem cells (ESCs), and it is becoming evident that regulation of protein degradation mediated by the ubiquitin–proteasome system (UPS) is one of the key cellular mechanisms in ESCs. Although the framework of that mechanism may seem simple, it involves complicated proteolytic machinery. The UPS controls cell development, survival, differentiation, lineage commitment, migration, and homing processes. This review is centered on the connection between stem cell factors NANOG, OCT-3/4, SOX2, KLF4, C-MYC, LIN28, FAK, and telomerase and the UPS. Herein, we summarize recent findings and discuss potential UPS mechanisms involved in pluripotency, reprogramming, differentiation, and self-renewal. Interactions between the UPS and stem cell transcription factors can apply to various human diseases which can be treated by generating more efficient iPSCs. Such complexes may permit the design of novel Therapeutics and the establishment of biomarkers that may be used in diagnosis and prognosis development. Therefore, the UPS is an important target for stem cell Therapeutic Product research.

  • Cellular functions of stem cell factors mediated by the ubiquitin–proteasome system
    Cellular and Molecular Life Sciences, 2018
    Co-Authors: Jihye Choi, Kwang-hyun Baek
    Abstract:

    Stem cells undergo partitioning through mitosis and separate into specific cells of each of the three embryonic germ layers: endoderm, mesoderm, and ectoderm. Pluripotency, reprogramming, and self-renewal are essential elements of embryonic stem cells (ESCs), and it is becoming evident that regulation of protein degradation mediated by the ubiquitin–proteasome system (UPS) is one of the key cellular mechanisms in ESCs. Although the framework of that mechanism may seem simple, it involves complicated proteolytic machinery. The UPS controls cell development, survival, differentiation, lineage commitment, migration, and homing processes. This review is centered on the connection between stem cell factors NANOG, OCT-3/4, SOX2, KLF4, C-MYC, LIN28, FAK, and telomerase and the UPS. Herein, we summarize recent findings and discuss potential UPS mechanisms involved in pluripotency, reprogramming, differentiation, and self-renewal. Interactions between the UPS and stem cell transcription factors can apply to various human diseases which can be treated by generating more efficient iPSCs. Such complexes may permit the design of novel Therapeutics and the establishment of biomarkers that may be used in diagnosis and prognosis development. Therefore, the UPS is an important target for stem cell Therapeutic Product research.

Jihye Choi - One of the best experts on this subject based on the ideXlab platform.

  • Cellular functions of stem cell factors mediated by the ubiquitin–proteasome system
    Cellular and Molecular Life Sciences, 2018
    Co-Authors: Jihye Choi, Kwang-hyun Baek
    Abstract:

    Stem cells undergo partitioning through mitosis and separate into specific cells of each of the three embryonic germ layers: endoderm, mesoderm, and ectoderm. Pluripotency, reprogramming, and self-renewal are essential elements of embryonic stem cells (ESCs), and it is becoming evident that regulation of protein degradation mediated by the ubiquitin–proteasome system (UPS) is one of the key cellular mechanisms in ESCs. Although the framework of that mechanism may seem simple, it involves complicated proteolytic machinery. The UPS controls cell development, survival, differentiation, lineage commitment, migration, and homing processes. This review is centered on the connection between stem cell factors NANOG, OCT-3/4, SOX2, KLF4, C-MYC, LIN28, FAK, and telomerase and the UPS. Herein, we summarize recent findings and discuss potential UPS mechanisms involved in pluripotency, reprogramming, differentiation, and self-renewal. Interactions between the UPS and stem cell transcription factors can apply to various human diseases which can be treated by generating more efficient iPSCs. Such complexes may permit the design of novel Therapeutics and the establishment of biomarkers that may be used in diagnosis and prognosis development. Therefore, the UPS is an important target for stem cell Therapeutic Product research.

  • Cellular functions of stem cell factors mediated by the ubiquitin–proteasome system
    Cellular and Molecular Life Sciences, 2018
    Co-Authors: Jihye Choi, Kwang-hyun Baek
    Abstract:

    Stem cells undergo partitioning through mitosis and separate into specific cells of each of the three embryonic germ layers: endoderm, mesoderm, and ectoderm. Pluripotency, reprogramming, and self-renewal are essential elements of embryonic stem cells (ESCs), and it is becoming evident that regulation of protein degradation mediated by the ubiquitin–proteasome system (UPS) is one of the key cellular mechanisms in ESCs. Although the framework of that mechanism may seem simple, it involves complicated proteolytic machinery. The UPS controls cell development, survival, differentiation, lineage commitment, migration, and homing processes. This review is centered on the connection between stem cell factors NANOG, OCT-3/4, SOX2, KLF4, C-MYC, LIN28, FAK, and telomerase and the UPS. Herein, we summarize recent findings and discuss potential UPS mechanisms involved in pluripotency, reprogramming, differentiation, and self-renewal. Interactions between the UPS and stem cell transcription factors can apply to various human diseases which can be treated by generating more efficient iPSCs. Such complexes may permit the design of novel Therapeutics and the establishment of biomarkers that may be used in diagnosis and prognosis development. Therefore, the UPS is an important target for stem cell Therapeutic Product research.

Ellen G. Feigal - One of the best experts on this subject based on the ideXlab platform.

  • Translation of Stem Cell Research: Points to Consider in Designing Preclinical Animal Studies
    Stem cells translational medicine, 2012
    Co-Authors: Joyce Frey-vasconcells, Kevin J. Whittlesey, Elona Baum, Ellen G. Feigal
    Abstract:

    Summary Stem cell-based therapies hold tremendous promise for the treatment of serious diseases and injuries. Although hematopoietic stem cell transplantation is routinely used as part of the treatment regime for some malignancies and genetic diseases, most stem cell-based Therapeutic Products are investigational and still require preclinical and clinical studies to support their many novel Therapeutic uses. Because of the multiple sources of stem cells, the plethora of potential applications, and the novel mechanism of action of stem cell-based therapies, there is no single set of universal guidance documents that can be used to inform the preclinical development path for these Therapeutics. Specific technical issues relating to the transplantation of human cells in animals, new delivery procedures, and laborious methods to characterize transplanted cells can present further challenges in the design and execution of preclinical animal studies for stem cell-based Therapeutic Products. In this article, we outline important parameters to guide the design of preclinical studies for stem cell-based Therapeutics. In addition, we review the types of preclinical studies that should be considered depending on the nature and specific use of the intended stem cell Therapeutic Product. Finally, we describe important considerations in the design and execution of specific studies to monitor the efficacy, toxicity, biodistribution, and tumorigenicity of stem cell-based Therapeutics.

Robin Thorpe - One of the best experts on this subject based on the ideXlab platform.

  • Strategies and assays for the assessment of unwanted immunogenicity
    Journal of Immunotoxicology, 2006
    Co-Authors: Meenu Wadhwa, Robin Thorpe
    Abstract:

    The assessment of unwanted immunogenicity associated with biological Products continues to be a major issue for the biotechnology industry. Monitoring of unwanted immunogenicity during the development of the Product from pre-clinical stage through clinical trials is now a regulatory expectation with extended post-marketing commitments required for at least some of these Products. Prospective planning of immunogenicity studies incorporating appropriately devised strategies is critical if valid conclusions concerning the immunogenicity profile of a Product are to be derived. An important consideration of such studies is the selection of optimized, rigorously validated and standardized methodologies for detection and characterization of antibodies with emphasis on desired assay design, assay controls, and performance criteria. Binding assays with different formats and detection systems, radioimmuno-precipitation assays or surface plasmon resonance procedures are often used as the basis for a screening assay. For assessing the neutralizing capacity of the antibodies, however, a neutralization assay is an absolute requirement. Therefore, a panel of methods is usually necessary for a detailed understanding of the type(s) of antibodies induced against a Therapeutic Product. This manuscript considers briefly the benefits and limitations of the different techniques available for antibody detection and characterization. A strategy that can be adopted for the assessment of unwanted immunogenicity of Therapeutic Products is also suggested.

  • strategies for detection measurement and characterization of unwanted antibodies induced by Therapeutic biologicals
    Journal of Immunological Methods, 2003
    Co-Authors: Meenu Wadhwa, C Bird, P Dilger, Rose Gainesdas, Robin Thorpe
    Abstract:

    An important aspect of evaluating the safety of Therapeutic biologicals is the assessment of the unwanted immunogenicity of such biologicals in recipients. Properly planned immunogenicity studies with appropriately devised strategies are critical if valid conclusions concerning the unwanted immunogenicity are to be derived. Such studies need to be conducted using carefully selected and validated procedures. Several techniques are available for detection and measurement of immunogenicity including immunoassays, radioimmunoprecipitation assays (RIPAs), surface plasmon resonance (SPR) and bioassays. A combination of methods for characterization of the induced antibodies is usually necessary for a detailed understanding of the type(s) of antibodies generated against a Therapeutic Product. This review considers the benefits and limitations of the various techniques available for antibody detection and outlines a strategy for the assessment of unwanted immunogenicity of Therapeutic Products.

Joyce Frey-vasconcells - One of the best experts on this subject based on the ideXlab platform.

  • Translation of Stem Cell Research: Points to Consider in Designing Preclinical Animal Studies
    Stem cells translational medicine, 2012
    Co-Authors: Joyce Frey-vasconcells, Kevin J. Whittlesey, Elona Baum, Ellen G. Feigal
    Abstract:

    Summary Stem cell-based therapies hold tremendous promise for the treatment of serious diseases and injuries. Although hematopoietic stem cell transplantation is routinely used as part of the treatment regime for some malignancies and genetic diseases, most stem cell-based Therapeutic Products are investigational and still require preclinical and clinical studies to support their many novel Therapeutic uses. Because of the multiple sources of stem cells, the plethora of potential applications, and the novel mechanism of action of stem cell-based therapies, there is no single set of universal guidance documents that can be used to inform the preclinical development path for these Therapeutics. Specific technical issues relating to the transplantation of human cells in animals, new delivery procedures, and laborious methods to characterize transplanted cells can present further challenges in the design and execution of preclinical animal studies for stem cell-based Therapeutic Products. In this article, we outline important parameters to guide the design of preclinical studies for stem cell-based Therapeutics. In addition, we review the types of preclinical studies that should be considered depending on the nature and specific use of the intended stem cell Therapeutic Product. Finally, we describe important considerations in the design and execution of specific studies to monitor the efficacy, toxicity, biodistribution, and tumorigenicity of stem cell-based Therapeutics.