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bone marrow transplantation, immunology

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https://www.readbyqxmd.com/read/28395110/murine-models-of-transplantation-tolerance-through-mixed-chimerism-advances-and-roadblocks
#1
REVIEW
Benedikt Mahr, Thomas Wekerle
Organ transplantation is the treatment of choice for patients with end-stage organ failure but chronic immunosuppression is taking its toll in terms of morbidity and poor efficacy in preventing late graft loss. Therefore a drug-free state would be desirable where the recipient permanently accepts a donor organ while remaining otherwise fully immunologically competent. Mouse studies unveiled mixed chimerism as an effective approach to deliberately induce such donor-specific tolerance and laid the foundation for a series of clinical pilot trials...
April 10, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28379044/advances-in-umbilical-cord-blood-cell-therapy-the-present-and-the-future
#2
Sofia Berglund, Isabelle Magalhaes, Ahmed Gaballa, Bruno Vanherberghen, Michael Uhlin
Umbilical cord blood (UCB), previously seen as medical waste, is increasingly recognized as a valuable source of cells for therapeutic use. The best-known application is in hematopoietic stem cell transplantation (HSCT), where UCB has become an increasingly important graft source in the 28 years since the first umbilical cord blood transplantation (UCBT) was performed. Recently, UCB has been increasingly investigated as a putative source for adoptive cell therapy. Areas covered: This review covers the advances in umbilical cord blood transplantation (UCBT) to overcome the limitation regarding cellular dose, immunological naivety and additional cell doses such as DLI...
April 5, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28373413/acute-graft-versus-host-disease-a-comprehensive-review
#3
REVIEW
Samah Nassereddine, Hind Rafei, Ehab Elbahesh, Imad Tabbara
Acute graft versus host disease (aGVHD) remains the second leading cause of death following allogeneic hematopoietic stem cell transplant (AHSCT). Over the last five years, the progress in understanding the pathophysiology of this immune based-process helped redefine graft versus host reaction and opened new possibilities for novel preventive and therapeutic approaches. The evolution in the field of immunology widened the horizons for hematopoietic stem cell transplant leading to the availability of different stem cell sources for potential graft and incorporation of novel conditioning regimens...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28368375/multiple-myeloma-patients-in-long-term-complete-response-after-autologous-stem-cell-transplantation-express-a-particular-immune-signature-with-potential-prognostic-implication
#4
A Arteche-López, A Kreutzman, A Alegre, P Sanz Martín, B Aguado, M González-Pardo, M Espiño, L M Villar, D García Belmonte, R de la Cámara, C Muñoz-Calleja
The proportion of multiple myeloma patients in long-term complete response (LTCR-MM) for more than 6 years after autologous stem cell transplantation (ASCT) is small. To evaluate whether this LTCR is associated with a particular immune signature, peripheral blood samples from 13 LTCR-MM after ASCT and healthy blood donors (HBD) were analysed. Subpopulations of T-cells (naïve, effector, central memory and regulatory), B-cells (naïve, marginal zone-like, class-switched memory, transitional and plasmablasts) and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry (MFC)...
April 3, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28367431/a-3-year-old-girl-with-recurrent-infections-and-autoimmunity-due-to-a-stat1-gain-of-function-mutation-the-expanding-clinical-presentation-of-primary-immunodeficiencies
#5
Juan Carlos Aldave Becerra, Enrique Cachay Rojas
We report a 3-year-old Peruvian girl, born to non-consanguineous parents. At the age of 8 months, she had a severe pneumonia complicated with empyema that required thoracic drainage and mechanical ventilation. Although no microorganisms were isolated, the patient recovered with broad-spectrum antibiotics. Since that date, she has presented multiple episodes of pneumonia and recurrent episodes of bronchospasm. At 1 year 5 months of age, the patient began with recurrent episodes of oropharyngeal, vaginal, and skin candidiasis, which improved transiently after using oral azole drugs...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28320105/anti-fibrotic-potential-of-human-umbilical-cord-mononuclear-cells-and-mouse-bone-marrow-cells-in-ccl4-induced-liver-fibrosis-in-mice
#6
Nageh Ahmed Elmahdy, Samia Salem Sokar, Mohamed Labib Salem, Naglaa Ibrahim Sarhan, Sherin Hamed Abou-Elela
Liver fibrosis is the consequence of hepatocyte injury that leads to the activation of hepatic stellate cells (HSC). The treatment of choice is Liver transplantation; however, it has many problems such as surgery-related complications, immunological rejection and high costs associated with the procedure. Stem cell-based therapy would be a potential alternative, so the aim of this study is to investigate the therapeutic potential of human umbilical cord mononuclear cells (MNC) and mouse bone marrow cells (BMC) against carbon tetrachloride (CCl4) induced liver fibrosis in mice and compare it with that of silymarin...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319446/good-laboratory-practice-preclinical-safety-studies-for-gsk2696273-mlv-vector-based-ex-vivo-gene-therapy-for-adenosine-deaminase-deficiency-severe-combined-immunodeficiency-in-nsg-mice
#7
Nicola Carriglio, Jan Klapwijk, Raisa Jofra Hernandez, Michela Vezzoli, Franck Chanut, Rhiannon Lowe, Draghici Elena, Melanie Nord, Paola Albertini, Patrizia Cristofori, Jane Richards, Hazel Staton, Jonathan Appleby, Alessandro Aiuti, Aisha V Sauer
GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28319074/tregs-hype-or-hope-for-allogeneic-hematopoietic-stem-cell-transplantation
#8
REVIEW
F Lussana, M Di Ianni, A Rambaldi
The discovery of T regulatory cells has been one of the most important advances in basic immunology and has opened the door to the development of innovative therapeutic strategies for improving the outcome of solid organ and hematopoietic stem cell transplantation. Basic immunology is rapidly elucidating the complex biology of these cells even though the difficulties in purifying or even expanding them in vitro represent a major limitation to the development of clinical studies. The clinical benefit potentially associated with this therapeutic approach remains to be demonstrated...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28251801/origin-of-enriched-regulatory-t-cells-in-patients-receiving-combined-kidney-bone-marrow-transplantation-to-induce-transplantation-tolerance
#9
B Sprangers, S DeWolf, T M Savage, T Morokata, A Obradovic, S A LoCascio, B Shonts, J Zuber, S P Lau, R Shah, H Morris, V Steshenko, E Zorn, F I Preffer, S Olek, D M Dombkowski, L A Turka, R Colvin, R Winchester, T Kawai, M Sykes
We examined tolerance mechanisms in patients receiving HLA-mismatched combined kidney-bone marrow transplantation (CKBMT) that led to transient chimerism under a previously published nonmyeloablative conditioning regimen (Immune Tolerance Network study 036). Polychromatic flow cytometry and high-throughput sequencing of T cell receptor-β hypervariable regions of DNA from peripheral blood regulatory T cells (Tregs) and CD4 non-Tregs revealed marked early enrichment of Tregs (CD3(+) CD4(+) CD25(high) CD127(low) Foxp3(+) ) in blood that resulted from peripheral proliferation (Ki67(+) ), possibly new thymic emigration (CD31(+) ), and, in one tolerant subject, conversion from non-Tregs...
March 1, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28210842/uric-acid-as-a-novel-biomarker-for-bone-marrow-function-and-incipient-hematopoietic-reconstitution-after-aplasia-in-patients-with-hematologic-malignancies
#10
Sebastian P Haen, Vicky Eyb, Nora Mirza, Aline Naumann, Andreas Peter, Markus W Löffler, Christoph Faul, Wichard Vogel, Wolfgang A Bethge, Hans-Georg Rammensee, Lothar Kanz, Martin Heni
PURPOSE: Prolonged aplasia and graft failure (GF) represent life-threatening complications after hematopoietic cell transplantation (HCT) requiring suitable biomarkers for early detection and differentiation between GF and poor graft function (PGF). Uric acid (UA) is a strong immunological danger signal. METHODS: Laboratory results were analyzed from patients undergoing either allogeneic or autologous HCT or induction chemotherapy for acute leukemia (n = 50 per group, n = 150 total)...
May 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#11
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28180000/haematopoietic-stem-cells-past-present-and-future
#12
REVIEW
Ashley P Ng, Warren S Alexander
The discovery and characterisation of haematopoietic stem cells has required decades of research. The identification of adult bone marrow as a source of haematopoietic cells capable of protecting an organism from otherwise lethal irradiation led to the intense search for their identity and characteristics. Using functional assays along with evolving techniques for isolation of haematopoietic cells, haematopoietic stem cell populations were able to be enriched and their characteristics analysed. The key haematopoietic stem cell characteristics of pluripotentiality and the ability for self-renewal have emerged as characteristics of several haematopoietic stem cell populations, including those that have recently challenged the conventional concepts of the haematopoietic hierarchy...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28147358/hematopoietic-stem-cell-transplantation-in-crohn-s-disease-state-of-the-art-treatment
#13
REVIEW
C J Hawkey
Both autologous and allogeneic haemopoietic stem cell transplantation (HSCT) have been tried in Crohn's disease (CD). In allogeneic HSCT, the host bone marrow is ablated and replaced by bone marrow from a donor. This substitution of a genetically different bone marrow is effective in a number of conditions including those with an immunological basis such as CD. While the toxicity of allogeneic HSCT has precluded its uptake in idiopathic CD, there is interest in its utility in the management of early onset infantile (inflammatory bowel disease), which behaves as a monogenic disorder, with abnormalities of the interleukin 10 signalling system as the best recognized...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28133783/prognostic-impact-of-the-cd34-cd38-cell-burden-in-patients-with-acute-myeloid-leukemia-receiving-allogeneic-stem-cell-transplantation
#14
Madlen Jentzsch, Marius Bill, Deedra Nicolet, Sabine Leiblein, Karoline Schubert, Martina Pless, Ulrike Bergmann, Kathrin Wildenberger, Luba Schuhmann, Michael Cross, Wolfram Pönisch, Georg-Nikolaus Franke, Vladan Vucinic, Thoralf Lange, Gerhard Behre, Krzysztof Mrózek, Clara D Bloomfield, Dietger Niederwieser, Sebastian Schwind
In acute myeloid leukemia (AML), leukemia-initiating cells exist within the CD34+/CD38- cell compartment. They are assumed to be more resistant to chemotherapy, enriched in minimal residual disease cell populations, and responsible for relapse. Here we evaluated clinical and biological associations and the prognostic impact of a high diagnostic CD34+/CD38- cell burden in 169 AML patients receiving an allogeneic stem cell transplantation in complete remission. Here, the therapeutic approach is mainly based on immunological graft-versus-leukemia effects...
April 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28007665/cd25-blockade-delays-regulatory-t-cell-reconstitution-and-does-not-prevent-graft-versus-host-disease-after-allogeneic-hematopoietic-cell-transplantation
#15
Frederick L Locke, Joseph Pidala, Barry Storer, Paul J Martin, Michael A Pulsipher, Thomas R Chauncey, Niels Jacobsen, Nicolaus Kröger, Irwin Walker, Susan Light, Bronwen E Shaw, Francisca Beato, Ginna G Laport, Auayporn Nademanee, Armand Keating, Gerard Socie, Claudio Anasetti
Daclizumab, a humanized monoclonal antibody, binds CD25 and blocks formation of the IL-2 receptor on T cells. A study of daclizumab as acute graft-versus-host disease (GVHD) prophylaxis after unrelated bone marrow transplantation was conducted before the importance of CD25(+)FOXP3(+) regulatory T cells (Tregs) was recognized. Tregs can abrogate the onset of GVHD. The relation between Tregs and a graft-versus-malignancy effect is not fully understood. An international, multicenter, double-blind clinical trial randomized 210 adult or pediatric patients to receive 5 weekly doses of daclizumab at 0...
December 19, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27998825/hematopoietic-arginase-1-deficiency-results-in-decreased-leukocytosis-and-increased-foam-cell-formation-but-does-not-affect-atherosclerosis
#16
Baoyan Ren, Erik Van Kampen, Theo J C Van Berkel, Sheena M Cruickshank, Miranda Van Eck
BACKGROUND AND AIMS: Arginase1 (Arg1), an M2 macrophage marker, plays a critical role in a number of immunological functions in macrophages, which are the main cell type facilitating atherosclerotic lesion development. Arg1 uses the substrate l-arginine to create l-ornithine, a precursor molecule required for collagen formation and vascular smooth muscle cell differentiation. By reducing l-arginine availability, Arg1 limits the production of nitric oxide (NO), a pro-atherogenic factor in macrophages...
January 2017: Atherosclerosis
https://www.readbyqxmd.com/read/27974567/human-cytomegalovirus-requires-epidermal-growth-factor-receptor-signaling-to-enter-and-initiate-the-early-steps-in-the-establishment-of-latency-in-cd34-human-progenitor-cells
#17
Jung Heon Kim, Donna Collins-McMillen, Jason C Buehler, Felicia D Goodrum, Andrew D Yurochko
The establishment of human cytomegalovirus (HCMV) latency and persistence relies on the successful infection of hematopoietic cells, which serve as sites of viral persistence and contribute to viral spread. Here, using blocking antibodies and pharmacological inhibitors, we document that HCMV activation of the epidermal growth factor receptor (EGFR) and downstream phosphatidylinositol 3-kinase (PI3K) mediates viral entry into CD34(+) human progenitor cells (HPCs), resulting in distinct cellular trafficking and nuclear translocation of the virus compared to that in other immune cells, such as we have documented in monocytes...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27881982/milestones-of-hematopoietic-stem-cell-transplantation-from-first-human-studies-to-current-developments
#18
REVIEW
Mateja Kralj Juric, Sakhila Ghimire, Justyna Ogonek, Eva M Weissinger, Ernst Holler, Jon J van Rood, Machteld Oudshoorn, Anne Dickinson, Hildegard T Greinix
Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation (HSCT) has become an established curative treatment for an increasing number of patients with life-threatening hematological, oncological, hereditary, and immunological diseases. This has become possible due to worldwide efforts of preclinical and clinical research focusing on issues of transplant immunology, reduction of transplant-associated morbidity, and mortality and efficient malignant disease eradication. The latter has been accomplished by potent graft-versus-leukemia (GvL) effector cells contained in the stem cell graft...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27879593/triptolide-reduces-the-required-dose-of-tacrolimus-by-attenuating-inflammation-enhancing-immunosuppression-and-increasing-donor-chimerism-in-a-heterotopic-hindlimb-transplantation-model
#19
Chuan Gu, Fei Liu, Xusong Luo, Xianyu Zhou, Jun Yang, L Scott Levin
BACKGROUND: Induction of tolerance and minimizing the toxicity of immunosuppression are two fundamental goals in vascularized composite allotransplantation. Accumulating data indicate that triptolide is an agent that may have the capacity to suppress inflammation and immunologic rejection. METHODS: A heterotopic hindlimb allotransplantation model from Brown Norway to Lewis rats was established and treated with different doses of tacrolimus combined with or without triptolide...
December 2016: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/27860293/thrombocytopenia-in-chronic-liver-disease
#20
REVIEW
Markus Peck-Radosavljevic
Thrombocytopenia is a common haematological disorder in patients with chronic liver disease. It is multifactorial and severity of liver disease is the most influential factor. As a result of the increased risk of bleeding, thrombocytopenia may impact upon medical procedures, such as surgery or liver biopsy. The pathophysiology of thrombocytopenia in chronic liver disease has long been associated with the hypothesis of hypersplenism, where portal hypertension causes pooling and sequestration of all corpuscular elements of the blood, predominantly thrombocytes, in the enlarged and congested spleen...
November 17, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
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