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bone marrow transplantation, immunology

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https://www.readbyqxmd.com/read/27881982/milestones-of-hematopoietic-stem-cell-transplantation-from-first-human-studies-to-current-developments
#1
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
#2
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
#3
Markus Peck-Radosavljevic
Thrombocytopenia is a common haematological disorder in patients with chronic liver disease (CLD). It is multifactorial and severity of liver disease is the most influential factor. Due to the increased risk of bleeding, thrombocytopenia may impact upon medical procedures, such as surgery or liver biopsy. The pathophysiology of thrombocytopenia in CLD 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
https://www.readbyqxmd.com/read/27859595/recipient-bone-marrow-derived-stromal-cells-prolong-graft-survival-in-a-rat-hind-limb-allotransplantation-model
#4
Ryosuke Ikeguchi, Ryosuke Kakinoki, Souichi Ohta, Hiroki Oda, Hirofumi Yurie, Yukitoshi Kaizawa, Hiroto Mitsui, Tomoki Aoyama, Junya Toguchida, Shuichi Matsuda
BACKGROUND: Recent studies have indicated that bone marrow-derived stromal cells (BMSCs) have immunomodulatory properties that suppress the T cell responses that cause graft rejection. The purpose of this study is to evaluate the effect of recipient BMSCs intravenous infusion for immunomodulation in a rat vascularized composite allotransplantation model. METHODS: A total of nine Wistar (WIS) rats and thirty Lewis (LEW) rats were used. BMSCs were harvested from three LEW rats...
November 17, 2016: Microsurgery
https://www.readbyqxmd.com/read/27855369/effect-of-extracellular-vesicles-on-neural-functional-recovery-and-immunologic-suppression-after-rat-cerebral-apoplexy
#5
Beilei Hu, Songfang Chen, Ming Zou, Zhiyong He, Shengmin Shao, Baohua Liu
BACKGROUND: Previous studies have demonstrated that mesenchymal stem cells (MSCs) can promote the recovery of neural function after cerebral apoplexy by secreting multiple cytokines. In addition, cell factor-derived extracellular vesicles play an important role in recovery of neural function. The aim of this study was to determine the effect of extracellular vesicles on neural functional recovery and brain tissue remodeling after cerebral apoplexy in a rat model. METHODS: The rat models with local ischemic stroke was established and three random groups were created...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27847830/early-differentiation-of-human-cd11c-nk-cells-with-%C3%AE-%C3%AE-t-cell-activation-properties-is-promoted-by-dialyzable-leukocyte-extracts
#6
Dalia Ramírez-Ramírez, Eduardo Vadillo, Lourdes Andrea Arriaga-Pizano, Héctor Mayani, Sergio Estrada-Parra, Marco Antonio Velasco-Velázquez, Sonia Mayra Pérez-Tapia, Rosana Pelayo
Reconstitution of the hematopoietic system during immune responses and immunological and neoplastic diseases or upon transplantation depends on the emergent differentiation of hematopoietic stem/progenitor cells within the bone marrow. Although in the last decade the use of dialyzable leukocyte extracts (DLE) as supportive therapy in both infectious and malignant settings has increased, its activity on the earliest stages of human hematopoietic development remains poorly understood. Here, we have examined the ability of DLE to promote replenishment of functional lymphoid lineages from CD34(+) cells...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27824136/lrba-is-essential-for-allogeneic-responses-in-bone-marrow-transplantation
#7
Mi Young Park, Raki Sudan, Neetu Srivastava, Sudha Neelam, Christie Youngs, Jia-Wang Wang, Robert W Engelman, William G Kerr
The PH-BEACH-WD40 (PBW) protein family members play a role in coordinating receptor signaling and intracellular vesicle trafficking. LPS-Responsive-Beige-like Anchor (LRBA) is a PBW protein whose immune function remains elusive. Here we show that LRBA-null mice are viable, but exhibit compromised rejection of allogeneic, xenogeneic and missing self bone-marrow grafts. Further, we demonstrate that LRBA-null Natural Killer (NK) cells exhibit impaired signaling by the key NK activating receptors, NKp46 and NKG2D...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27812432/treatment-of-rapidly-progressive-systemic-sclerosis-current-and-futures-perspectives
#8
Fabian A Mendoza, Maryah Mansoor, Sergio A Jimenez
INTRODUCTION: Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by severe and often progressive cutaneous, pulmonary, cardiac and gastrointestinal tract fibrosis, cellular and humoral immunologic alterations, and pronounced fibroproliferative vasculopathy. There is no effective SSc disease modifying therapy. Patients with rapidly progressive SSc have poor prognosis with frequent disability and very high mortality. AREAS COVERED: This paper reviews currently available therapeutic approaches for rapidly progressive SSc and discuss novel drugs under study for SSc disease modification...
2016: Expert Opinion on Orphan Drugs
https://www.readbyqxmd.com/read/27779901/identification-and-characterization-of-a-dendritic-cell-precursor-in-parenchymal-lung-tissue
#9
Christophe von Garnier, Fabian Blank, Barbara Rothen-Rutishauser, Joachim R Goethert, Patrick G Holt, Philip A Stumbles, Deborah H Strickland
The pulmonary parenchymal and mucosal microenvironments are constantly exposed to the external environment and thus require continuous surveillance to maintain steady-state immunological homeostasis. This is achieved by a mobile network of pulmonary dendritic cells (DC) and macrophages (mø) that constantly sample and process microenvironmental antigens into signals that can initiate or dampen inflammation, either locally or after onward migration to draining lymph nodes. The constant steady-state turnover of pulmonary DC and mø requires replenishment from bone-marrow precursors, however the nature of the pulmonary precursor cell remains unclear, although recent studies suggest that subsets of pulmonary DC may derive from circulating monocytic precursors...
October 25, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27776691/combination-of-tacrolimus-and-mycophenolate-mofetil-induces-oxidative-stress-and-genotoxicity-in-spleen-and-bone-marrow-of-wistar-rats
#10
Hanen Ferjani, Hossam Draz, Salwa Abid, Abedellatif Achour, Hassen Bacha, Imen Boussema-Ayed
Tacrolimus (TAC) and mycophenolate mofetil (MMF) are common immunosuppressive drugs used to avoid immunological rejection of transplanted organs. The risk of developing cancer is the most critical complication in organ transplant recipients undergoing immunosuppressive therapy. This study aims to explore the cytotoxic and genotoxic effects of TAC and MMF alone or combined orally administrated on spleen and bone marrow of Wistar rats. Our results showed that TAC (2.4; 24 and 60mg/kg) and MMF (5; 50 and 125mg/kg) induced a genotoxic effect on rat bone marrow...
November 1, 2016: Mutation Research
https://www.readbyqxmd.com/read/27758159/comparison-of-human-hematopoietic-reconstitution-in-different-strains-of-immunodeficient-mice
#11
Ashley I Beyer, Marcus O Muench
Immunodeficient mice play a critical role in hematology research as in vivo models of hematopoiesis and immunology. Multiple strains have been developed, but hematopoietic stem cell engraftment and immune reconstitution have not been methodically compared among them. Four mouse strains were transplanted with human fetal bone marrow or adult peripheral blood CD34+ cells: NSG, NSG-3GS, hSCF-Tg-NSG and hSIRPα-DKO. Hematopoietic engraftment in the bone marrow, blood, spleen and liver was evaluated by flow cytometry 12 weeks after transplant...
October 19, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27748733/adoptively-transferred-donor-il-17-producing-cd4-t-cells-augment-but-il-17-alleviates-acute-graft-versus-host-disease
#12
Yifeng Cai, Shoubao Ma, Yuejun Liu, Huanle Gong, Qiao Cheng, Bo Hu, Yan Wu, Xiao Yu, Chen Dong, Kai Sun, Depei Wu, Haiyan Liu
The role of IL-17 and IL-17-producing CD4(+) T cells in acute graft-versus-host disease (GVHD) has been controversial in recent mouse and human studies. We carried out studies in a murine acute GVHD model of fully major histocompatibility complex-mismatched myeloablative bone marrow transplantation. We showed that donor wild-type CD4(+) T cells exacerbated acute GVHD compared with IL-17(-/-) CD4(+) T cells, while IL-17 reduced the severity of acute GVHD. The augmentation of acute GVHD by transferred donor IL-17-producing CD4(+) T cells was associated with increased Th1 responses, while IL-17 decreased the percentages of Th1 cells in the GVHD target organs...
October 17, 2016: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/27717379/biohybrid-cochlear-implants-in-human-neurosensory-restoration
#13
Ariane Roemer, Ulrike Köhl, Omid Majdani, Stephan Klöß, Christine Falk, Sabine Haumann, Thomas Lenarz, Andrej Kral, Athanasia Warnecke
BACKGROUND: The success of cochlear implantation may be further improved by minimizing implantation trauma. The physical trauma of implantation and subsequent immunological sequelae can affect residual hearing and the viability of the spiral ganglion. An ideal electrode should therefore decrease post-implantation trauma and provide support to the residual spiral ganglion population. Combining a flexible electrode with cells producing and releasing protective factors could present a potential means to achieve this...
October 7, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27695456/immunological-basis-of-bone-marrow-failure-after-allogeneic-hematopoietic-stem-cell-transplantation
#14
Stavroula Masouridi-Levrat, Federico Simonetta, Yves Chalandon
Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27695454/induction-of-hematopoietic-microchimerism-by-gene-modified-bmt-elicits-antigen-specific-b-and-t-cell-unresponsiveness-toward-gene-therapy-products
#15
Jérémie Martinet, Gwladys Bourdenet, Amine Meliani, Laetitia Jean, Sahil Adriouch, Jose L Cohen, Federico Mingozzi, Olivier Boyer
BACKGROUND: Gene therapy is a promising treatment option for hemophilia and other protein deficiencies. However, immune responses against the transgene product represent an obstacle to safe and effective gene therapy, urging for the implementation of tolerization strategies. Induction of a hematopoietic chimerism via bone marrow transplantation (BMT) is a potent means for inducing immunological tolerance in solid organ transplantation. OBJECTIVES: We reasoned, here, that the same viral vector could be used, first, to transduce BM cells for inducing chimerism-associated transgene-specific immune tolerance and, second, for correcting protein deficiencies by vector-mediated systemic production of the deficient coagulation factor...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27653226/comparative-study-of-the-immunoregulatory-capacity-of-in-vitro-generated-tolerogenic-dendritic-cells-suppressor-macrophages-and-myeloid-derived-suppressor-cells
#16
Laura Carretero-Iglesia, Laurence Bouchet-Delbos, Cédric Louvet, Lucile Drujont, Mercedes Segovia, Emmanuel Merieau, Elise Chiffoleau, Régis Josien, Marcelo Hill, Maria-Cristina Cuturi, Aurélie Moreau
BACKGROUND: Regulatory myeloid cell (RMC) therapy is a promising strategy for the treatment of immunological disorders such as autoimmune disease and allograft transplant rejection. Various RMC subsets can be derived from total bone marrow using different protocols, but their phenotypes often overlap, raising questions about whether they are truly distinct. METHODS: In this study, we directly compared the phenotype and function of 3 types of RMCs, tolerogenic dendritic cells, suppressor macrophages, and myeloid-derived suppressor cells, generated in vitro from the same mouse strain in a single laboratory...
October 2016: Transplantation
https://www.readbyqxmd.com/read/27646791/the-effect-of-cyclophosphamide-on-the-immune-system-implications-for-clinical-cancer-therapy
#17
REVIEW
Martina Ahlmann, Georg Hempel
Cyclophosphamide is an alkylating agent belonging to the group of oxazaphosporines. As cyclophosphamide is in clinical use for more than 40 years, there is a lot of experience using this drug for the treatment of cancer and as an immunosuppressive agent for the treatment of autoimmune and immune-mediated diseases. Besides antimitotic and antireplicative effects, cyclophosphamide has immunosuppressive as well as immunomodulatory properties. Cyclophosphamide shows selectivity for T cells and is therefore now frequently used in tumour vaccination protocols and to control post-transplant allo-reactivity in haplo-identical unmanipulated bone marrow after transplantation...
October 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27638617/immunological-considerations-for-treating-globoid-cell-leukodystrophy
#18
REVIEW
Subha Karumuthil-Melethil, Steven J Gray
Globoid cell leukodystrophy (GLD, or Krabbe's disease) is a severe inherited neurodegenerative disease caused by the lack of a lysosomal enzyme, GALC. The disease has been characterized in humans as well as three naturally occurring animal models, murine, canine, and nonhuman primate. Multiple treatment strategies have been explored for GLD, including enzyme replacement therapy, small-molecule pharmacological approaches, gene therapy, and bone marrow transplant. No single therapeutic approach has proved to be entirely effective, and the reason for this is not well understood...
November 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27524270/immunological-properties-of-bone-marrow-microenvironment-1%C3%A2-year-after-allogeneic-hematopoietic-stem-cell-transplantation
#19
Agnieszka Ciomber, Iwona Mitrus, Wojciech Fidyk, Andrzej Smagur, Agata Chwieduk, Magdalena Glowala-Kosinska, Tomasz Czerw, Małgorzata Sobczyk-Kruszelnicka, Włodzimierz Mendrek, Maria Sadus-Wojciechowska, Jacek Najda, Jerzy Holowiecki, Sebastian Giebel
Regeneration of the bone marrow microenvironment after transplantation of allogeneic hematopoietic stem cells is poorly explored. The goal of our study was to investigate this process focusing on immunologic factors: concentrations of selected cytokines, expression of immunosuppressive proteins CD47 and CD274 on hematopoietic stem cells, and frequency of T regulatory lymphocytes (Tregs). Bone marrow samples were collected before transplantation, on the day of transplantation, and at the 1-year follow-up. As a control group, we used bone marrow from healthy donors...
August 12, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27518974/transplantation-of-hamster-xenogeneic-tissue-in-syngeneic-murine-chimaeras
#20
J B Bridges, J K Houston
CBA mice exposed to an otherwise lethal dose of irradiation (1006 rads) were saved by the intravenous injection of suspensions of CBA bone marrow cells. Hamster kidney cells (BHK) were injected intraperitoneally into these mice at 1, 3, 7 and 14 days after irradiation and marrow injection. The injected cells survived and proliferated in the abdominal cavities of the mice. The cells invaded abdominal organs and the skeletal muscle of the body wall. Mice injected with BHK cells 24 hours after irradiation and marrow injection survived 11-23 days...
December 1975: Irish Journal of Medical Science
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