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Cellular Therapies (cellular + therapy)
Selected AbstractsAdult stem cell plasticity: will engineered tissues be rejected?INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2004Te-Chao Fang Summary The dogma that adult tissue-specific stem cells remain committed to supporting only their own tissue has been challenged; a new hypothesis, that adult stem cells demonstrate plasticity in their repertoires, is being tested. This is important because it seems possible that haematopoietic stem cells, for example, could be exploited to generate and perhaps deliver cell-based therapies deep within existing nonhaematopoietic organs. Much of the evidence for plasticity derives from histological studies of tissues from patients or animals that have received grafts of cells or whole organs, from a donor bearing (or lacking) a definitive marker. Detection in the recipient of appropriately differentiated cells bearing the donor marker is indicative of a switch in phenotype of a stem cell or a member of a transit amplifying population or of a differentiated cell. In this review, we discuss evidence for these changes occurring but do not consider the molecular basis of cell commitment. In general, the extent of engraftment is low but may be increased if tissues are damaged. In model systems of liver regeneration, the repeated application of a selection pressure increases levels of engraftment considerably; how this occurs is unclear. Cell fusion plays a part in regeneration and remodelling of the liver, skeletal muscle and even regions of the brain. Genetic disease may be amenable to some forms of cell therapy, yet immune rejection will present challenges. Graft- vs. -host disease will continue to present problems, although this may be avoided if the cells were derived from the recipient or they were tolerized. Despite great expectations for cellular therapies, there are indications that attempts to replace missing proteins could be confounded simply by the development of specific immunity that rejects the new phenotype. [source] Regulatory issues in cellular therapiesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S38 2002Adrian P. Gee, Article first published online: 23 APR 200 Cellular and gene therapies offer considerable promise as new treatment modalities. The Food and Drug Administration has been developing strategies to regulate these rapidly evolving fields in a manner that sustains progress and also ensures minimization of potential risks. The death of a patient on a gene therapy study highlighted a number of potential problems that have galvanized the agency to examine their strategy and to review current regulations for gene therapy. Meanwhile, a unified regulatory approach is emerging for cell-based therapies. This stratifies the level of regulation based upon the potential risk to the donor of the cells and the recipient. In this article the history and status of regulation of cellular therapy is briefly reviewed. J. Cell. Biochem. Suppl. 38: 104,112, 2002. © 2002 Wiley-Liss, Inc. [source] ISBT 128 implementation plan for cellular therapy productsJOURNAL OF CLINICAL APHERESIS, Issue 5 2007Paul Ashford Abstract The publication of new standards for terminology and labeling marks an important step in ensuring consistency and traceability of cellular therapies at the global level. However, it is only with the widespread implementation of the standard that the benefits can be truly realized. This paper provides guidance on the practical aspects of adopting these new standards for organizations with differing current levels of computerization. It discusses project management, equipment, licensing, and validation topics. J. Clin. Apheresis, 2007. © 2007 Internal Cellular Therapy Coding and Labeling Advisory Group. [source] Review article: Potential cellular therapies for renal disease: Can we translate results from animal studies to the human condition?NEPHROLOGY, Issue 6 2009MELISSA H LITTLE SUMMARY The incidence of chronic kidney disease is increasing worldwide, prompting considerable research into potential regenerative therapies. These have included studies to determine whether an endogenous renal stem cell exists in the postnatal kidney and whether non-renal adult stem cells, such as mesenchymal stem cell, can ameliorate renal damage. Such stem cells will either need to be recruited to the damaged kidney to repair the damage in situ or be differentiated into the desired cell type and delivered into the damaged kidney to subsequently elicit repair without maldifferentiation. To date, these studies have largely been performed using experimental and genetic models of renal damage in rodents. The translation of such research into a therapy applicable to human disease faces many challenges. In this review, we examine which animal models have been used to evaluate potential cellular therapies and how valid these are to human chronic kidney disease. [source] Translating Sleeping Beauty transposition into cellular therapies: Victories and challengesBIOESSAYS, Issue 9 2010Zsuzsanna Izsvák Abstract Recent results confirm that long-term expression of therapeutic transgenes can be achieved by using a transposon-based system in primary stem cells and in vivo. Transposable elements are natural DNA transfer vehicles that are capable of efficient genomic insertion. The latest generation, Sleeping Beauty transposon-based hyperactive vector (SB100X), is able to address the basic problem of non-viral approaches , that is, low efficiency of stable gene transfer. The combination of transposon-based non-viral gene transfer with the latest improvements of non-viral delivery techniques could provide a long-term therapeutic effect without compromising biosafety. The new challenges of pre-clinical research will focus on further refinement of the technology in large animal models and improving the safety profile of SB vectors by target-selected transgene integration into genomic "safe harbors." The first clinical application of the SB system will help to validate the safety of this approach. [source] Microarray-based gene expression analysis as a process characterization tool to establish comparability of complex biological products: Scale-up of a whole-cell immunotherapy productBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2009Min Wang Abstract Whole-cell immunotherapies and other cellular therapies have shown promising results in clinical trials. Due to the complex nature of the whole cell product and of the sometimes limited correlation of clinical potency with the proposed mechanism of action, these cellular immunotherapy products are generally not considered well characterized. Therefore, one major challenge in the product development of whole cell therapies is the ability to demonstrate comparability of product after changes in the manufacturing process. Such changes are nearly inevitable with increase in manufacturing experience leading to improved and robust processes that may have higher commercial feasibility. In order to comprehensively assess the impact of the process changes on the final product, and thus establish comparability, a matrix of characterization assays (in addition to lot release assays) assessing the various aspects of the cellular product are required. In this study, we assessed the capability of DNA-microarray-based, gene-expression analysis as a characterization tool using GVAX cancer immunotherapy cells manufactured by Cell Genesys, Inc. The GVAX immunotherapy product consists two prostate cancer cell lines (CG1940 and CG8711) engineered to secrete human GM-CSF. To demonstrate the capability of the assay, we assessed the transcriptional changes in the product when produced in the presence or absence of fetal bovine serum, and under normal and hypoxic conditions, both changes intended to stress the cell lines. We then assessed the impact of an approximately 10-fold process scale-up on the final product at the transcriptional level. These data were used to develop comparisons and statistical analyses suitable for characterizing culture reproducibility and cellular product similarity. Use of gene-expression data for process characterization proved to be a reproducible and sensitive method for detecting differences due to small or large changes in culture conditions as might be encountered in process scale-up or unanticipated bioprocess failures. Gene expression analysis demonstrated that cell products of representative lots under the same production process and at the same production scale were statistically identical. Large process changes that resulted from the artificial stress conditions used (absence of FBS and induction of hypoxia) displayed profoundly different gene expression patterns. We propose the use of simple t -test analysis in combination with the herein introduced expression ratio with mean intensity (ERMI) analysis as useful tools for process characterization by global gene expression analysis. Biotechnol. Bioeng. 2009; 104: 796,808 © 2009 Wiley Periodicals, Inc. [source] Transdifferentiation in developmental biology, disease, and in therapyDEVELOPMENTAL DYNAMICS, Issue 12 2007Shifaan Thowfeequ Abstract Transdifferentiation (or metaplasia) refers to the conversion of one cell type to another. Because transdifferentiation normally occurs between cells that arise from the same region of the embryo, understanding the molecular and cellular events in cell type transformations may help to explain the mechanisms underlying normal development. Here we review examples of transdifferentiation in nature focusing on the possible role of cell type switching in metamorphosis and regeneration. We also examine transdifferentiation in mammals in relation to disease and the use of transdifferentiated cells in cellular therapy. Developmental Dynamics 236:3208,3217, 2007. © 2007 Wiley-Liss, Inc. [source] Regulatory issues in cellular therapiesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S38 2002Adrian P. Gee, Article first published online: 23 APR 200 Cellular and gene therapies offer considerable promise as new treatment modalities. The Food and Drug Administration has been developing strategies to regulate these rapidly evolving fields in a manner that sustains progress and also ensures minimization of potential risks. The death of a patient on a gene therapy study highlighted a number of potential problems that have galvanized the agency to examine their strategy and to review current regulations for gene therapy. Meanwhile, a unified regulatory approach is emerging for cell-based therapies. This stratifies the level of regulation based upon the potential risk to the donor of the cells and the recipient. In this article the history and status of regulation of cellular therapy is briefly reviewed. J. Cell. Biochem. Suppl. 38: 104,112, 2002. © 2002 Wiley-Liss, Inc. [source] Immunotherapy using autologous monocyte-derived dendritic cells pulsed with leukemic cell lysates for acute myeloid leukemia relapse after autologous peripheral blood stem cell transplantationJOURNAL OF CLINICAL APHERESIS, Issue 2 2004Je-Jung Lee Abstract Although a second stem cell transplantation (SCT) can be used as salvage therapy in patients with relapsing leukemia after SCT, most of these patients have a poor outcome. We tried clinical vaccination using monocyte-derived dendritic cells (DCs) pulsed with leukemic lysates to treat relapsing acute myeloid leukemia (AML) after autologous SCT. To generate DCs, CD14+ cells isolated from peripheral blood stem cell products were cultured in AIM-V in the presence of GM-CSF and IL-4. Adding TNF-, on day 6 induced maturation of the DCs, which were harvested on day 8 or 9. The DCs were incubated with tumor lysate and KLH for 2 hr at 37°C. After certifying the absence of microorganisms and endotoxins, the patients received four DC vaccinations at two- to three-week intervals. Two patients received four DC vaccinations with means of 7.8 × 106 and 9 × 106 DCs at two- to three-week intervals. The DC vaccinations were well tolerated with no apparent side effects. After the vaccinations, the patients showed immunological responses with positive delayed-type hypersensitivity skin reaction and increasing autologous T cells stimulatory capacity to the DCs; however, the BM blast percentage of the patients did not improve. The results suggest that DCs are a feasible cellular therapy for relapsing AML after autologous SCT. J Clin Apheresis 19:66,70, 2004. © 2004 Wiley-Liss, Inc. [source] Muscle-derived Stem Cell Therapy for Stress Urinary IncontinenceLUTS, Issue 2009Shing-Hwa LU The aim of the present article is to overview the potential of muscle-derived stem cells and other cellular therapy for urethral regeneration and to review the clinical experiences of its application in patients with stress urinary incontinence. [source] Mesenchymal stem cells: Immunobiology and therapeutic potential in kidney disease (Review Article)NEPHROLOGY, Issue 1 2007STEVEN J MCTAGGART SUMMARY: Mesenchymal stem cells (MSC) are non-haematopoietic cells that are prevalent in the adult bone marrow but can also be isolated from a variety of other postnatal tissues. MSC are non-immunogenic and are immunosuppressive, with the ability to inhibit maturation of dendritic cells and suppress the function of naďve and memory T cells, B cells and NK cells. In addition to their immunomodulatory properties, MSC are capable of differentiating into various tissues of mesenchymal and non-mesenchymal origin and migrating to sites of tissue injury and inflammation to participate in tissue repair. A number of studies in animal models of cardiac injury, stroke and ischaemic renal injury have demonstrated the clinical potential of MSC in tissue regeneration and repair. MSC are currently being evaluated in various preclinical and clinical studies in humans and offer significant potential as a novel cellular therapy for tissue regeneration and immunological conditions. The present review focuses on the unique immunomodulatory and regenerative properties of MSC and their potential role in the treatment of kidney disease. [source] Cytokine stimulation and the choice of promoter are critical factors for the efficient transduction of mouse T cells with HIV-1 vectorsTHE JOURNAL OF GENE MEDICINE, Issue 2 2010David E. Gilham Abstract Background HIV-1 fails to successfully infect mouse T cells as a result of several blocks in the viral replication cycle. We investigated whether this also impacted on the use of HIV-1 derived lentiviral vectors for stable gene transfer into mouse T cells. Methods Freshly isolated primary mouse T cells were immediately mixed with lentiviral vectors encoding an enhanced green fluorescent protein marker gene and transduction frequency was determined after 5 days of culture. Results Optimal transduction required both mouse T cell activation and cytokine support. Furthermore, transduction was also dependent upon the promoter chosen, with the rank order of potency being PGK > EF1 > SFFV > CMV. HIV-1 lentiviral vectors also efficiently transduced cytokine-stimulated T cells (in the absence of antibody driven T cell activation), albeit with a lower level of transgene expression compared to fully-activated T cells. Conclusions The present study demonstrates that primary mouse T cells can be efficiently transduced with HIV-1 lentiviral vectors, opening up prospects for their use in mouse models of gene-modified adoptive cellular therapy. Copyright © 2009 John Wiley & Sons, Ltd. [source] | |||||||||||||