Download or read book Identification and Characterization of Human Hematopoietic Stem Cells Using Gene Transfer and the Novel SCID Transplantation Assay written by André Larochelle and published by . This book was released on 1997 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The absence of preclinical repopulation assays for primitive human hematopoietic cells has hindered the development of stem cell gene therapy. Current human gene therapy trials employ gene transfer methods optimized using surrogate in vitro colony-forming cell (CFC) and longterm culture-initiating cell (LTC-IC) assays and by inference from studies on other mammalian species. In this thesis, we report the identification and characterization of a novel human hematopoietic cell, capable of repopulating the bone marrow (BM) of nonobese diabetic mice with severe combined immunodeficiency (NOD/SCID), namely the SCID-repopulating cell (SRC). Human BM or cord blood (CB) cells were infected with retroviral vectors and subsequently transplanted into NOD/SCID mice. Whereas CFC and LTC-IC were efficiently transduced with retroviruses, SRCs were transduced rarely, establishing that SRC are biologically distinct from most CFC and LTC-IC. Moreover, characterization of the cell surface phenotype indicated that SRC are exclusively CD3$\sp+$CD38$\sp-$ in contrast to CFC and LTC-IC that are mostly found in the CD34$\sp+$CD38$\sp+$ fraction after multiparameter flow sorting, confirming the distinct character of SRC. In combination with various data obtained in the past decade, these analyses provide the strongest evidence that SRC defines a novel human hematopoietic cell that is more immature than any other cell type detected to date. The inefficient infection of SRC was consistent with the low level of gene marking reported in primates and human gene therapy trials. This inability to infect the most primitive human repopulating cells, in contrast to most CFC and LTC-IC, highlights the need for appropriate pre-clinical models that will predict the outcomes of human clinical trials. As described in chapter 3 of this thesis, primitive BM cells from $\beta$-thalassemia major and sickle cell anemia (SCA) patients can engraft and proliferate in the BM of immune-deficient mice. The BM of transplanted mice contained the entire erythroid lineage from BFU-E to mature erythrocytes expressing human $\gamma$-, $\beta$- or $\rm\beta\sp{s}$-globin as in the original donor. Moreover, human erythroid cells from mice transplanted with SCA bone marrow showed characteristic sickling under reducing conditions in an in vitro assay. This system can thus be used to evaluate gene transfer efficiency into primitive human cells, longevity of expression, expression in the appropriate lineage, and correction of the disease phenotype.

Download or read book Identification and Characterization of Human Hematopoietic Stem Cells Using Gene Transfer and the Novel SCID Transplantation Assay written by and published by . This book was released on 1997 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Hematopoietic Stem Cell Transplantation written by Anthony D. Ho and published by CRC Press. This book was released on 2000-07-25 with total page 610 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book integrates recent advances in molecular and cell biology of hematopoietic stem cells (HSC) with developments in clinical research in stem cell-based therapy-providing an up-to-date review of novel cytokines and cellular components; animal models; cell preparation, selection, and collection; minimal residual disease and purging; expansion

Download or read book Identification and Characterization of Novel Regulators of Hematopoietic Stem Cell Fate written by Eric Matthew Mendenhall and published by . This book was released on 2006 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Stem Cells from Cord Blood in Utero Stem Cell Development and Transplantation Inclusive Gene Therapy written by W. Holzgreve and published by Springer Science & Business Media. This book was released on 2013-03-09 with total page 265 pages. Available in PDF, EPUB and Kindle. Book excerpt: The title "Stem Cells from Cord Blood, In Utero Stem Cell Develop ment, and Transplantation-Inclusive Gene Therapy" suggests that more than one topic is combined in one workshop. Indeed, at first glance the recovery of stem cells from cord blood has to be seen as separate from the attempts to achieve effective in utero therapy by stem cell trans plantation, because the first issue deals with an innovative stem cell source as an alternative to bone marrow, which is already spreading rapidly in medical practice, whereas the second topic is still strictly ex perimental and only investigated in medical centers with the appropri ate background. It is, however, not only justified, but helpful to com bine the two topics in one workshop and consequently to cover them in the same volume of the Ernst Schering Research Foundation Work shop series, because they are intimately related and both based on the new insights into the biology of stem cells. Professor Werner Arber, the Nobel Laureate from the University of Basel, pointed out in his In- Professor Dr. W. Holzgreve VI Preface The participants of the workshop troductory Lecture that our understanding of hematopoietic stem cells as descendents of totipotent cells and our current approaches to using them in post-and prenatal therapy have been furthered significantly by genetic engineering technologies which are "artificial contributions to the process of biologic evolution".

Download or read book Discovery and Functional Analysis of Novel Determinants of Hematopoietic Stem and Progenitor Cell Function written by Craig Evan Eckfeldt and published by . This book was released on 2005 with total page 314 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Thomas Hematopoietic Cell Transplantation 2 Volume Set written by Stephen J. Forman and published by John Wiley & Sons. This book was released on 2016-12-27 with total page 1789 pages. Available in PDF, EPUB and Kindle. Book excerpt: Fully revised for the fifth edition, this outstanding reference on bone marrow transplantation is an essential, field-leading resource. Extensive coverage of the field, from the scientific basis for stem-cell transplantation to the future direction of research Combines the knowledge and expertise of over 170 international specialists across 106 chapters Includes new chapters addressing basic science experiments in stem-cell biology, immunology, and tolerance Contains expanded content on the benefits and challenges of transplantation, and analysis of the impact of new therapies to help clinical decision-making Includes a fully searchable Wiley Digital Edition with downloadable figures, linked references, and more References for this new edition are online only, accessible via the Wiley Digital Edition code printed inside the front cover or at www.wiley.com/go/forman/hematopoietic.

Download or read book Hematopoietic Stem Cells written by Christa Müller-Sieburg and published by Springer. This book was released on 1992 with total page 278 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Characterization of the Human Hematopoietic Stem Cell Compartment written by Joby Leigh McKenzie and published by . This book was released on 2007 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: The hematopoietic system is structured as a hierarchy sustained by rare hematopoietic stem cells (HSCs), which are able to regenerate the blood for the lifetime of an animal through balanced self-renewal and differentiation divisions. HSCs possess the cardinal stem cell properties of longterm (LT) proliferation, multilineage differentiation and self-renewal capacity, and must be functionally assayed for their ability to repopulate the hematopoietic system of transplant recipients. The most commonly utilized assay for human hematopoietic cells is the immune-deficient NOD/SCID xenotransplant model. Primitive human cells that are able to repopulate NOD/SCID mice are operationally defined as SCID-repopulating cells (SRCs). In this thesis, I describe modifications to the conventional NOD/SCID xenotransplant model, including further immune-depletion by treating mice with an anti-CD122 (IL-2Rbeta) antibody that eliminates natural killer cells and macrophages, as well as direct delivery of hematopoietic cells into the marrow cavity of the femur. This model provides a more permissive environment for SRCs, supporting high-level human cell engraftment and evaluation of self-renewal in serial recipients. Lentiviral marking enabled tracking of the self-renewal behaviours of individual SRCs derived from Lin--, Lin --CD34+CD38-- and Lin --CD34+CD38lo populations. Over 600 clones were evaluated over the course of 3 to 7 months. Some clones extinguished in primary recipients, other clones were able to self-renew, while a subset of clones were activated from a quiescent state upon secondary transplantation revealing that SRCs are heterogeneous with respect to longevity and self-renewal potential. In order to gain an understanding of molecular mechanisms regulating HSC self-renewal, pure populations of cells are needed. Therefore, we exploited Rhodamine 123 (Rho) as a functional marker of HSCs in combination with the Lin--CD34+CD38-- immunophenotype. LT self-renewing HSCs resided within the Rholo fraction at a frequency of 1 SRC in 30 Lin--CD34+CD38 --Rholo cells. Furthermore, the use of functional markers is important as we demonstrated a dissociation in phenotype and function as expression of CD38 on the cell surface of Lin--CD34 + SRCs reverses from a negative to a low state without loss of stem cell capacity. Collectively, these studies have helped to provide further insight into human HSC biology.

Download or read book Gene Transfer Into Hemopoietic Stem Cells written by Markus Peter Wilhelmus Einerhand and published by . This book was released on 1992 with total page 108 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book High Dose Therapy and Transplantation of Haemopoietic Stem Cells written by Wolfgang Schultze and published by Wiley-Blackwell. This book was released on 2000 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book summarizes the most recent findings in the field of high-dose therapy of malignant & non-malignant diseases, both in basic & clinical research. Newly developed methods are included, & emphasis is placed on acute & chronic myeloid & lymphocytic leukemia, multiple myeloma, myelodysplastic syndromes, aplastic anemia & autoimmune disease, & certain solid tumors.

Download or read book Stem Cell Transplantation written by Anthony Ho and published by Wiley-Blackwell. This book was released on 2006-08-25 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is the first handbook on the whole field of stem cell research covering (1) molecular and cellular fundamentals, (2) clinical applications and (3) GMP processing. It provides a timely overview of the potential and plasticity of adult stem cells. With its focus on standardization and quality control of cell lines suited for processing and clinical trials, the book features novel therapeutic approaches that offer great promise for new ways of treating neural, hematological and cardiovascular diseases. The editors are leading international experts in adult stem cell research, and their successful networking in the US and Europe has resulted in a distinguished team of authors from around the world.

Download or read book Human Hematopoietic Stem Cells Ex Vivo Expansion Gene Transfer and Molecular Characterization written by Yuk Yin Ng and published by . This book was released on 2003 with total page 132 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Characterization of the Biology of Normal and Leukemic Human Hematopoietic Stem Cells microform written by Jean Chuen Yi Wang and published by Library and Archives Canada = Bibliothèque et Archives Canada. This book was released on 2005 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt: Studies in murine hematopoiesis have demonstrated that the hematopoietic system is a hierarchy maintained by rare self-renewing pluripotent hematopoietic stem cells (HSC). Long-term in vivo repopulation assays are the only definitive means by which to identify and characterize HSC. Research in human hematopoiesis has advanced significantly since the development of xenotransplantation assays using immune-deficient mouse recipients to detect primitive human hematopoietic cells with in vivo repopulating ability (SCID-repopulating cells, SRC). Here we establish the quantitative nature of the SRC assay, and use this assay to purify SRC based on surface marker expression, achieving a 1,500-fold enrichment within the Lin - CD34+CD38- fraction. Combined with gene transfer techniques to uniquely mark the progeny of individual SRC, these developments have facilitated detailed analysis of the clonal behaviour of human HSC, and have led to the demonstration of functional heterogeneity within the human stem cell compartment. Recent studies have shown that human myeloid leukemia is also hierarchical and is sustained in vivo by rare leukemia stem cells (LSC). As with normal HSC, in vivo assays are required to study the unique biology of LSC. Here we develop an in vivo model for chronic myelogenous leukemia (CML) that allows characterization of CML stem cells and assessment of the contribution of secondary genetic changes to leukemic progression in this disease. Complementary in vitro systems modelled in primary human cells enable examination of the molecular events that occur during leukemogenesis. Here we report the transformation and immortalization of normal human hematopoietic cells following initiation of a pre-leukemic program by TLS-ERG expression. Our findings provide direct evidence for multiple cooperating events in leukemogenesis, and demonstrate the usefulness of this system for studying leukemic initiation and progression. We have also investigated the role of telomerase in normal and leukemic hematopoiesis. We demonstrate that telomerase overexpression fails to extend the replicative lifespan of human hematopoietic cells unless normal developmental pathways are disrupted. Elevated telomerase activity does not prevent telomere shortening even in transformed hematopoietic cells, implying tighter regulation of telomere length dynamics compared to other somatic cell types. Our findings further suggest that telomerase itself may contribute to leukemic progression.

Download or read book Assessment and Improvement of Gene Transfer Into Human Hematopoietic Stem Cells written by Dimitri Anthonius Breems and published by . This book was released on 1997 with total page 164 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Bone Marrow Transplantation in Children written by Frank Leonard Johnson and published by . This book was released on 1990 with total page 570 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The EBMT Handbook written by Nicolaus Kröger and published by . This book was released on 2020-10-08 with total page 688 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Open Access edition of the European Society for Blood and Marrow Transplantation (EBMT) handbook addresses the latest developments and innovations in hematopoietic stem cell transplantation and cellular therapy. Consisting of 93 chapters, it has been written by 175 leading experts in the field. Discussing all types of stem cell and bone marrow transplantation, including haplo-identical stem cell and cord blood transplantation, it also covers the indications for transplantation, the management of early and late complications as well as the new and rapidly evolving field of cellular therapies. This book provides an unparalleled description of current practices to enhance readers' knowledge and practice skills. This work was published by Saint Philip Street Press pursuant to a Creative Commons license permitting commercial use. All rights not granted by the work's license are retained by the author or authors.