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T-cells, bone marrow transplant

Yawara Kawano, Oksana Zavidij, Jihye Park, Michele Moschetta, Katsutoshi Kokubun, Tarek H Mouhieddine, Salomon Manier, Yuji Mishima, Naoka Murakami, Mark Bustoros, Romanos Sklavenitis Pistofidis, Mairead Reidy, Yu J Shen, Mahshid Rahmat, Pavlo Lukyanchykov, Esilida Sula Karreci, Shokichi Tsukamoto, Jiantao Shi, Satoshi Takagi, Daisy Huynh, Antonio Sacco, Yu-Tzu Tai, Marta Chesi, P Leif Bergsagel, Aldo M Roccaro, Jamil Azzi, Irene M Ghobrial
Despite significant advances in the treatment of multiple myeloma (MM), most patients succumb to disease progression. One of the major immunosuppressive mechanisms that is believed to play a role in myeloma progression, is the expansion of regulatory T-cells (Tregs). In this study, we demonstrate that myeloma cells drive Treg expansion and activation by secreting type-1 interferon (IFN). Blocking IFNAR1 (interferon alpha and beta receptor 1) on Tregs significantly decreases both, myeloma-associated Treg immunosuppressive function and myeloma progression...
March 20, 2018: Journal of Clinical Investigation
Sinem Civriz Bozdağ, Meltem Kurt Yüksel, Taner Demirer
Stem cells can be either totipotent, pluripotent, multipotent or unipotent. Totipotent cells have the capability to produce all cell types of the developing organism, including both embryonic and extraembryonic tissues. The Hematopoietic Stem Cells (HSC) are the first defined adult stem cells (ASC) that give rise to all blood cells and immune system. Use of HSCs for treatment of hematologic malignancies, which is also called bone marrow (BM) transplantation or peripheral blood stem cells (PBSC) transplantation is the pioneer of cellular therapy and translational research...
March 20, 2018: Advances in Experimental Medicine and Biology
Naoya Ishibashi, Tatsuaki Watanabe, Masahiko Kanehira, Yui Watanabe, Yasushi Hoshikawa, Hirotsugu Notsuda, Masafumi Noda, Akira Sakurada, Shinya Ohkouchi, Takashi Kondo, Yoshinori Okada
PURPOSE: Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. METHODS: Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation...
March 15, 2018: Surgery Today
Adam Gassas, Ponni Sivaprakasam, Michelle Cummins, Patricia Breslin, Katharine Patrick, Mary Slatter, Roderick Skinner, Geof Shenton, Brenda Gibson, Sarah Lawson, Toni Petterson, Michael Potter, Beki James, Rachael Hough, Prashant Hiwarkar, Ajay Vora, Paul Veys, Josu De La Fuente, Robert Wynn, Persis Amrolia
Paediatric therapy-related acute myeloid leukaemia (t-AML) is rare and the outcome is poor. While allogeneic haematopoietic stem cell transplantation (HSCT) is generally the accepted modality of treatment, data regarding salvage chemotherapy, remission induction, conditioning regimens, transplant-related mortality and outcome is scarce. Between 2000 and2016, 36 children with t-AML were treated in seven UK paediatric HSCT centres. The most common salvage protocol for remission induction was FLAG with or without idarubicin and 28 patients were in complete morphological remission prior to BMT...
March 15, 2018: Bone Marrow Transplantation
Corinna Schmitz, Heidi Noels, Omar El Bounkari, Eva Straussfeld, Remco T A Megens, Marieke Sternkopf, Setareh Alampour-Rajabi, Christine Krammer, Pathricia V Tilstam, Norbert Gerdes, Christina Bürger, Aphrodite Kapurniotu, Richard Bucala, Joachim Jankowski, Christian Weber, Jürgen Bernhagen
The inflammatory cytokine macrophage migration-inhibitory factor (MIF) promotes atherosclerosis via lesional monocyte and T-cell recruitment. B cells have emerged as important components in atherogenesis, but the interaction between MIF and B cells in atherogenesis is unknown. Here, we investigated the atherosclerotic phenotype of Mif-gene deletion in Apoe-/- mice. Apoe-/- Mif-/- mice on a Western-diet exhibited strongly reduced atherosclerotic lesions in brachiocephalic artery (BC) and abdominal aorta compared with controls...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Lisa M Sharkey, Sarah Peacock, Neil K Russell, Stephen J Middleton, Andrew J Butler
Graft versus host disease (GVHD) following transplantation of an intestine-containing graft occurs more frequently than with other solid organ transplants and is known to have a poor outcome. The presentation differs from other solid organ transplants, as the gastrointestinal tract is not involved following intestinal transplant. Diagnosis is based on clinical symptoms arising due to native tissue damage and the detection of donor T lymphocytes in circulating blood (T cell chimerism). The ideal treatment strategy has not been defined, with advocates for both increased or decreased immunosuppression...
March 15, 2018: Clinical Transplantation
Jingyi Li, Jie Xu, Lynne V Abruzzo, Guilin Tang, Shaoying Li, M James You, Gary Lu, Elias J Jabbour, Qi Deng, Carlos E Bueso-Ramos, L Jeffrey Medeiros, C Cameron Yin
We describe the clinical, morphologic, immunophenotypic and molecular genetic features of 15 cases of acute myeloid leukemia (AML) with t(4;12)(q12;p13). There were 9 men and 6 women, with a median age of 50 years (range, 17-76). Most patients had hypercellular bone marrow with a median blast count of 58% and multilineage dysplasia. Flow cytometry analysis showed myeloid lineage with blasts positive for CD13, CD33, CD34, CD38, CD117 and HLA-DR. Interestingly, aberrant CD7 expression was detected in 12/14 cases, and myeloperoxidase was either negative (3/15) or positive in only a small subset of the blasts (12/15)...
February 16, 2018: Oncotarget
Coco de Koning, Julie-Anne Gabelich, Jurgen Langenhorst, Rick Admiraal, Jurgen Kuball, Jaap Jan Boelens, Stefan Nierkens
Residual antithymocyte globulin (ATG; Thymoglobulin) exposure after allogeneic hematopoietic (stem) cell transplantation (HCT) delays CD4+ T-cell immune reconstitution (CD4+ IR), subsequently increasing morbidity and mortality. This effect seems particularly present after cord blood transplantation (CBT) compared to bone marrow transplantation (BMT). The reason for this is currently unknown. We investigated the effect of active-ATG exposure on CD4+ IR after BMT and CBT in 275 patients (CBT n = 155, BMT n = 120; median age, 7...
March 13, 2018: Blood Advances
Reginald M Gorczynski, Nuray Erin, Tahir Maqbool, Christopher P Gorczynski, Laura Y Gorczynski
BACKGROUND AND PURPOSE: In BALB/c mice with transplantable breast tumors, we showed that CD200R1KO mice were cured of local and metastatic growth of EMT6 cells following surgical resection of localized tumor and immunization with irradiated cells along with CpG as adjuvant. On the other hand, wild-type (WT) animals treated in the same fashion develop pulmonary and liver metastases within 20 days of surgery. To develop an in vitro system which would mimic the in vivo model and allow exploration of factors controlling tumor invasion as a precursor to in vivo metastasis, we have developed and characterized a two-phase culture system...
March 12, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Yongxia Wu, Steven Schutt, Katelyn Paz, Mengmeng Zhang, Ryan P Flynn, David Bastian, M Hanief Sofi, Hung Nguyen, Min Dai, Chen Liu, Ying-Jun Chang, Bruce R Blazar, Xue-Zhong Yu
Chronic graft-versus-host disease (cGVHD) is characterized as autoimmune-like fibrosis and antibody production mediated by pathogenic T-cells and B-cells. MicroRNA (miR)-17-92 influences the survival, differentiation and function of lymphocytes in cancer, infections and autoimmunity. To determine whether miR-17-92 regulates T- and B-cell responses in cGVHD, we generated mice conditionally deficient for miR-17-92 in T-cells, B-cells, or both. Using murine models of allogeneic bone marrow transplantation (allo-BMT), we demonstrate that expression of miR-17-92 in donor T- and B-cells is essential for the induction of both scleroderma and bronchiolitis obliterans in cGVHD...
March 12, 2018: Blood
Mallika Ghosh, Shobha Thangada, Oisharya Dasgupta, Kamal M Khanna, Harold T Yamase, Michael Kashgarian, Timothy Hla, Linda H Shapiro, Fernando A Ferrer
Sphingosine Kinase-2 (Sphk2) is responsible for the production of the bioactive lipid Sphingosine-1 Phosphate, a key regulator of tissue repair. Here we address the in vivo significance of Sphingosine Kinase -2 in renal inflammation/fibrosis in response to unilateral ureteral obstruction using both genetic and pharmacological strategies. Obstructed kidneys of Sphk2-/- mice showed reduced renal damage and diminished levels of the renal injury markers TGFβ1 and αSMA when compared to wild type controls. We found a consistently significant increase in anti-inflammatory (M2) macrophages in obstructed Sphk2-/- kidneys by flow cytometry and a decrease in mRNA levels of the inflammatory cytokines, MCP1, TNFα, CXCL1 and ILβ1, suggesting an anti-inflammatory bias in the absence of Sphk2...
2018: PloS One
Tiziano Barbui, Ayalew Tefferi, Alessandro M Vannucchi, Francesco Passamonti, Richard T Silver, Ronald Hoffman, Srdan Verstovsek, Ruben Mesa, Jean-Jacques Kiladjian, Rȕdiger Hehlmann, Andreas Reiter, Francisco Cervantes, Claire Harrison, Mary Frances Mc Mullin, Hans Carl Hasselbalch, Steffen Koschmieder, Monia Marchetti, Andrea Bacigalupo, Guido Finazzi, Nicolaus Kroeger, Martin Griesshammer, Gunnar Birgegard, Giovanni Barosi
This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) published in 2011 by the European LeukemiaNet (ELN) consortium. Recommendations were produced by multiple-step formalized procedures of group discussion. A critical appraisal of evidence by using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was performed in the areas where at least one randomized clinical trial was published. Seven randomized controlled trials provided the evidence base; earlier phase trials also informed recommendation development...
February 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Pingnan Xiao, Monika Dolinska, Lakshmi Sandhow, Makoto Kondo, Anne-Sofie Johansson, Thibault Bouderlique, Ying Zhao, Xidan Li, Marios Dimitriou, George Z Rassidakis, Eva Hellström-Lindberg, Nagahiro Minato, Julian Walfridsson, David T Scadden, Mikael Sigvardsson, Hong Qian
Mutations of signal-induced proliferation-associated gene 1 ( SIPA1 ), a RAP1 GTPase-activating protein, were reported in patients with juvenile myelomonocytic leukemia, a childhood myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Sipa1 deficiency in mice leads to the development of age-dependent MPN. However, Sipa1 expression in bone marrow (BM) microenvironment and its effect on the pathogenesis of MPN remain unclear. We here report that Sipa1 is expressed in human and mouse BM stromal cells and downregulated in these cells from patients with MPN or MDS/MPN at diagnosis...
March 13, 2018: Blood Advances
Shinji Okano, Kareem Abu-Elmagd, Danielle D Kish, Karen Keslar, William M Baldwin, Robert L Fairchild, Masato Fujiki, Ajai Khanna, Mohammed Osman, Guilherme Costa, John Fung, Charles Miller, Hiroto Kayashima, Koji Hashimoto
Recent advances in immunosuppressive regimens have decreased acute cellular rejection (ACR) rates and improved intestinal transplant (ITx) recipient survival. We investigated the role of myeloid-derived suppressor cells (MDSCs) in ITx. We identified MDSCs as CD33+ CD11b+ lineage(CD3/CD56/CD19)- HLA-DR-/low cells with 3 subsets, CD14- CD15- (e-MDSC), CD14+ CD15- (M-MDSC), and CD14- CD15+ (PMN-MDSC), in peripheral blood mononuclear cells (PBMCs) and mononuclear cells in the grafted intestinal mucosa. Total MDSC numbers increased in PBMCs following ITx; among MDSC subsets, M-MDSC numbers were maintained at high level after 2 months following ITx...
March 6, 2018: American Journal of Transplantation
Jianwu Chen, Dongliang Zhang, Tao Zhang, Chen Chen, Yajuan Song, Shiqiang Liu, Yingjun Su, Shuzhong Guo
BACKGROUND: Vascularized composite allograft (VCA), such as hand and face allograft, contains a vascularized bone component that may provide an immunologic benefit and induce tolerance for the simultaneous inclusion of marrow cells and a marrow microenvironment. We developed a chimeric groin cutaneous/femur flap to investigate the effect of vascularized bone marrow on VCA survival and its ability to induce chimerism. METHODS: Brown Norway and Lewis rats were used as donors and recipients, respectively...
April 2018: Journal of Surgical Research
Xin Qing, Annie Qing, Ping Ji, Samuel W French, Holli Mason
BACKGROUND: Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the Philadelphia (Ph) chromosome generated by the reciprocal translocation t(9,22)(q34;q11). The natural progression of the disease follows a biphasic or triphasic course. Most cases of CML are diagnosed in the chronic phase. Extramedullary blast crisis rarely occurs during the course of CML, and is extremely rare as the initial presentation of CML. CASE PRESENTATION: Here, we report the case of a 32-year-old female with enlarged neck lymph nodes and fatigue...
March 1, 2018: Experimental and Molecular Pathology
Yuhui Lin
Accelerated failure time (AFT) model is commonly applied in engineering studies to address the failure rate of a machine. In humans, survival profile of transplant patients is among the rare scenarios whereby AFT is applicable. To date, it is uncertain whether reliable risk estimates and age-specific mortality trajectories have been published using conventional statistics approach. By investigating mortality trajectory, the rate of aging d(log(μ(x)))/dx of Hematopoietic Stem Cells Transplants (HSCTs) patients who had underwent first-allogeneic transplants can be obtained, and to unveil the possibility of elasticity of human aging rate in HSCTs...
2018: PloS One
Fei Hua, Yueqiu Chen, Ziying Yang, Xiaomei Teng, Haoyue Huang, Zhenya Shen
BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) could exert a potent immunosuppressive effect, and therefore may have a therapeutic potential in T-cell-dependent pathologies. We aimed to examine the effects of BMSCs on immune tolerance of allogeneic heart transplantation and the involvement of CD45RB+ dendritic cells (DCs). METHODS: Bone marrow-derived DCs and BMSCs were co-cultured, with CD45RB expression on the surface of DCs measured by flow cytometry...
February 28, 2018: Clinical Transplantation
Sonja Krohn, Jasper F Nies, Sonja Kapffer, Tilman Schmidt, Jan-Hendrik Riedel, Anna Kaffke, Anett Peters, Alina Borchers, Oliver M Steinmetz, Christian F Krebs, Jan-Eric Turner, Silke R Brix, Hans-Joachim Paust, Rolf A K Stahl, Ulf Panzer
The IL-17 cytokine family and the cognate receptors thereof have a unique role in organ-specific autoimmunity. Most studies have focused on the founding member of the IL-17 family, IL-17A, as the central mediator of diseases. Indeed, although pathogenic functions have been ascribed to IL-17A and IL-17F in the context of immune-mediated glomerular diseases, the specific functions of the other IL-17 family members in immunity and inflammatory kidney diseases is largely unknown. Here, we report that compared with healthy controls, patients with acute Anti-neutrophil cytoplasmatic antibody (ANCA)-associated crescentic glomerulonephritis (GN) had significantly elevated serum levels of IL-17C (but not IL-17A, F, or E)...
February 26, 2018: Journal of the American Society of Nephrology: JASN
Timothy J Abram, Curtis R Pickering, Alexander K Lang, Nancy E Bass, Rameez Raja, Cynthia Meena, Amin M Alousi, Jeffrey N Myers, John T McDevitt, Ann M Gillenwater, Nadarajah Vigneswaran
Fanconi anemia (FA) is a hereditary genomic instability disorder with a predisposition to leukemia and oral squamous cell carcinomas (OSCCs). Hematopoietic stem cell transplantation (HSCT) facilitates cure of bone marrow failure and leukemia and thus extends life expectancy in FA patients; however, survival of hematologic malignancies increases the risk of OSCC in these patients. We developed a "cytology-on-a-chip" (COC)-based brush biopsy assay for monitoring patients with oral potentially malignant disorders (OPMDs)...
February 23, 2018: Translational Oncology
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