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Hematopoietic stem cells

Alborz Karimzadeh, Vanessa M Scarfone, Erika Varady, Connie Chao, Karin Grathwohl, John W Fathman, David A Fruman, Thomas Serwold, Matthew A Inlay
Hematopoietic stem cells (HSCs) are the self-renewing multipotent progenitors to all blood cell types. Identification and isolation of HSCs for study has depended on the expression of combinations of surface markers on HSCs that reliably distinguish them from other cell types. However, the increasing number of markers required to isolate HSCs has made it tedious, expensive, and difficult for newcomers, suggesting the need for a simpler panel of HSC markers. We previously showed that phenotypic HSCs could be separated based on expression of CD11a and that only the CD11a negative fraction contained true HSCs...
March 15, 2018: Stem Cells Translational Medicine
Kotoe Iesato, Tsukasa Hori, Yuko Yoto, Masaki Yamamoto, Natsuko Inazawa, Kenichi Kamo, Hiroshi Ikeda, Satoshi Iyama, Naoki Hatakeyama, Akihiro Iguchi, Junichi Sugita, Ryoji Kobayashi, Nobuhiro Suzuki, Hiroyuki Tsutsumi
BACKGROUND: Patients undergoing hematopoietic stem cell transplantation (HSCT) frequently experience HHV-6 reactivation typically during early phase following HSCT. However, the long-term clinical complications and prognosis among such patients remain unclear. METHODS: Between September 2010 and October 2012, whole blood samples from 105 patients collected weekly from prior to 6 weeks after HSCT underwent multiplex polymerase chain reaction (PCR) to screen for viral DNA, followed by real-time PCR for quantitative estimation...
March 14, 2018: Pediatrics International: Official Journal of the Japan Pediatric Society
Kevin Rakszawski, Kosuke Miki, David Claxton, Henry Wagner, Hiroko Shike, Shin Mineishi, Seema Naik
Approximately 30-40% of patients with acute myeloid leukemia (AML) experience induction failures. In these patients who do not achieve remission with two cycles of standard induction therapies, the probability of achieving remission with subsequent inductions is very limited. Hematopoietic stem cell transplantation (HSCT) is the only curative option for these patients, but high relapse rate and transplant-related mortality often preclude them to proceed to transplant. Thus, AML not in remission at time of HSCT remains a huge unmet need in current HSCT practice, particularly if the patient does not have an HLA-matched donor identified by the time of two induction failures...
March 14, 2018: International Journal of Hematology
Xingxing Yu, Lingling Xu, Yingjun Chang, Xiaojun Huang, Xiangyu Zhao
The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Th1, Th2, Th3 and Tr1 cells. Here, we investigate levels of type 1 (IFN-gamma; NK1), type 2 (IL-13; NK2), type 3 (TGF-beta; NK3) and regulatory (IL-10; NKr) cytokines in peripheral blood to assess the cytokine profiles of natural killer (NK) cells following human allogeneic hematopoietic stem cell transplantation (allo-HSCT). NK2 and NK3 cell expansion was observed after allo-HSCT; levels of NKr cells reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT...
March 9, 2018: Science China. Life Sciences
Qian Li, Xiao-Ji Lin, Hui Chen, Jian Gong, Zhen Li, Xiang-Nan Chen
More than 90% of patients with chronic myeloid leukemia (CML) have the chromosomal translocation t(9;22)(q34;q11), while 5-8% of patients have complex variant translocations that have previously been thought not to affect the efficacy of imatinib therapy. The present study reports a patient with CML in B-lymphoid blast crisis who had a rare three-way Philadelphia (Ph) variant t(3;9;22)(p21;q34;q11), in addition to isodicentric Ph chromosomes. The patient was initially treated with imatinib for >2 months with a very poor response...
April 2018: Oncology Letters
Antonella Mancusi, Sara Piccinelli, Andrea Velardi, Antonio Pierini
FoxP3+ regulatory T cells (Tregs) are a subset of CD4+ T cells that can suppress proliferation and effector functions of T cells, B cells, NK cells, and antigen-presenting cells. Treg deficiency causes dramatic immunologic disease in both animal models and humans. As they are capable to suppress the function and the proliferation of conventional CD4+ and CD8+ T cells, Treg-based cell therapies are under evaluation for the treatment of various autoimmune diseases and are currently employed to prevent graft-versus-host disease (GvHD) in clinical trials of hematopoietic stem cell transplantation...
2018: Frontiers in Immunology
Areej El-Jawahri, Sarah R Fishman, Julie Vanderklish, Don S Dizon, Nicole Pensak, Lara Traeger, Joseph A Greer, Elyse R Park, Netana Markovitz, Lauren Waldman, Chrisa Hunnewell, Meredith Saylor, Jessica Driscoll, Zhigang Li, Thomas R Spitzer, Steven McAfee, Yi-Bin Chen, Jennifer S Temel
BACKGROUND: Although sexual dysfunction is common after hematopoietic stem cell transplantation (HCT), interventions to address sexual function are lacking. METHODS: We conducted a pilot study to assess the feasibility and preliminary efficacy of a multimodal intervention to address sexual dysfunction in allogeneic HCT survivors. Transplant clinicians screened HCT survivors ≥3 months post-HCT for sexual dysfunction causing distress. Those who screened positive attended monthly visits with a trained transplant clinician who: 1) performed an assessment of the causes of sexual dysfunction; 2) educated and empowered the patient to address his or her sexual concerns; and 3) implemented therapeutic interventions targeting the patient's needs...
March 14, 2018: Cancer
Revathi Rajagopal, Marianne Phillips, Nicholas G Gottardo
The initial signs of hepatic sinusoidal obstruction syndrome (HSOS) can be challenging to recognize in children, especially outside the hematopoietic stem cell transplantation setting. To assist clinicians to promptly identify HSOS, the European Society for Blood and Marrow Transplantation has proposed pediatric HSOS diagnostic criteria which emphasize unexplained consumptive and transfusion-refractory thrombocytopenia. To highlight the importance of these "bellwether" early signs of HSOS and the efficacy of pre-emptive treatment with defibrotide, we describe the case of a child with a right 11th rib primitive neuroectodermal tumor who developed HSOS following focal radiotherapy and actinomycin-D treatment...
March 14, 2018: Pediatric Blood & Cancer
Arti Nanda, Maitham A A Husain, Waleed Al-Herz, Adla Almekaimi, Humoud Al-Sabah, Mohammad Al-Otaibi
BACKGROUND/OBJECTIVES: Allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment option for many life-threatening disorders in children. Chronic graft-versus-host disease (cGVHD) is a significant complication of HSCT, and its treatment is challenging. Skin is the most common organ affected in cGVHD, with protean manifestations posing a challenge in diagnosis and management. The objective was to have a better understanding of the spectrum of chronic cutaneous GVHD (cc-GVHD) in children...
March 14, 2018: Pediatric Dermatology
T Wang, M Remberger, U Axdorph Nygell, M Sundin, A Björklund, J Mattsson, M Uhlin, E Watz
BACKGROUND: The composition of the graft used for allogeneic hematopoietic stem cell transplantation (HSCT) is important for the treatment outcome. Different apheresis devices may yield significant differences in peripheral blood stem cell graft cellular composition. We compared stem cell grafts produced by Cobe Spectra (Cobe) and Spectra Optia (Optia) with use of the mononuclear cell (MNC) protocol, and evaluated clinical outcome parameters such as graft-versus-host disease (GvHD), transplant-related mortality (TRM), relapse, and overall survival...
March 13, 2018: Transfusion
Guy Laureys, Barbara Willekens, Ludo Vanopdenbosch, Olivier Deryck, Dominik Selleslag, Miguel D'Haeseleer, Ann De Becker, Bénédicte Dubois, Daan Dierickx, Gaetano Perrotta, Virginie De Wilde, Vincent van Pesch, Nicole Straetmans, Dominique Dive, Yves Beguin, Bart Van Wijmeersch, Koen Theunissen, Tessa Kerre, Ann Van de Velde
Multiple sclerosis is considered to be an immune mediated inflammatory disorder of the central nervous system. It mainly affects young, socioeconomic active patients. Although our armamentarium for this disease has significantly evolved in recent years some patients remain refractory to conventional therapies. In these cases, autologous hematopoietic stem cell transplantation can be considered as a therapeutic option. Decreasing morbidity, mortality, and increasing patient awareness have led to rising inquiry by our patients about this treatment option...
March 13, 2018: Acta Neurologica Belgica
Erico Masala, Ana Valencia-Martinez, Serena Pillozzi, Tommaso Rondelli, Alice Brogi, Alessandro Sanna, Antonella Gozzini, Annarosa Arcangeli, Persio Dello Sbarba, Valeria Santini
Myelodysplastic Syndromes (MDS) are clonal neoplasms where stem/progenitor cells endowed with self-renewal and capable of perpetuating the disease have been demonstrated. It is known that oxygen tension plays a key role in driving normal hematopoiesis and that hematopoietic stem cells are maintained in hypoxic areas of the bone marrow (BM). Hypoxia could also regulate leukemic/dysplastic hematopoiesis. We evaluated the stem cell potential of MDS cells derived from the BM of 39 MDS patients and selected under severe hypoxia...
February 13, 2018: Oncotarget
Shuping Peng, Lihua Cao, Shiwei He, Yancheng Zhong, Haotian Ma, Yanru Zhang, Cijun Shuai
Bone regeneration is very important for the recovery of some diseases including osteoporosis and bone fracture trauma. It is a multiple-step- and multiple-gene-involved complex process, including the matrix secretion and calcium mineralization by osteoblasts differentiated from mesenchymal stem cells (MSCs) and the absorption of calcium and phosphorus by osteoclasts differentiated from hematopoietic stem cells. Long noncoding RNAs (lncRNAs) are a family of transcripts longer than 200 nt without or with very low protein-coding potential...
2018: Stem Cells International
Thomas Magg, Tilmann Schober, Christoph Walz, Julia Ley-Zaporozhan, Fabio Facchetti, Christoph Klein, Fabian Hauck
Epstein-Barr virus positive (EBV+ ) smooth muscle tumors (SMTs) constitute a very rare oncological entity. They usually develop in the context of secondary immunodeficiency caused by human immunodeficiency virus infection or immunosuppressive treatment after solid organ transplantation. However, in a small fraction of predominantly pediatric patients, EBV+ SMTs may occur in patients with primary immunodeficiency disorders (PIDs), such as GATA2 and CARMIL2 deficiency. In secondary immunodeficiencies and when the underlying condition can not be cured, the treatment of EBV+ SMTs is based on surgery in combination with antiretroviral and reduced or altered immunosuppressive pharmacotherapy, respectively...
2018: Frontiers in Immunology
Xin Shi, Shengcai Wei, Kevin J Simms, Devan N Cumpston, Thomas J Ewing, Ping Zhang
Activation and reprogramming of hematopoietic stem/progenitor cells play a critical role in the granulopoietic response to bacterial infection. Our current study determined the significance of Sonic hedgehog (SHH) signaling in the regulation of hematopoietic precursor cell activity during the host defense response to systemic bacterial infection. Bacteremia was induced in male Balb/c mice via intravenous injection (i.v.) of Escherichia coli (5 × 107 CFUs/mouse). Control mice received i.v. saline. SHH protein level in bone marrow cell (BMC) lysates was markedly increased at both 24 and 48 h of bacteremia...
2018: Frontiers in Immunology
Hitomi Hosoya, Jeffrey Levine, Peter Abt, David Henry, David L Porter, Saar Gill
Sickle-cell disease (SCD) leads to recurrent vaso-occlusive crises, chronic end-organ damage, and resultant physical, psychological, and social disabilities. Although hematopoietic stem-cell transplantation (HSCT) is potentially curative for SCD, this procedure is associated with well-recognized morbidity and mortality and thus is ideally offered only to patients at high risk of significant complications. However, it is difficult to identify patients at high risk before significant complications have occurred, and once patients experience significant organ damage, they are considered poor candidates for HSCT...
March 13, 2018: Blood Advances
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
M Palova, T Szotkowski, A Hlusi, K Indrak, J Navratilova, M Divoka, T Papajik
Primary myelofibrosis (PMF) is a chronic clonal myeloid disorder. Together with essential thrombocythemia (ET) and polycythemia vera (PV), it belongs to a group of Philadelphia chromosome-negative myeloproliferative neoplasms. An integral part of laboratory tests carried out in this disease group is detecting the presence of mutations in the Janus kinase 2 gene at position 617 (JAK2 V617F) and in the gene encoding for the receptor for thrombopoietin (myeloproliferative leukemia virus oncogene, MPL) found in approximately 60% of PMF patients...
2018: Neoplasma
Takeshi Shimoide, Naoyuki Kawao, Yukinori Tamura, Kiyotaka Okada, Yoshitaka Horiuchi, Katsumi Okumoto, Shinji Kurashimo, Masayoshi Ishida, Kohei Tatsumi, Osamu Matsuo, Hiroshi Kaji
Delayed fracture healing is a significant clinical problem among various complications in diabetic patients. However, the details in the mechanisms of diabetic delayed bone repair have still remained unknown. Here, we investigated the roles of macrophages in diabetic delayed bone repair after femoral bone injury using streptozotocin (STZ)-treated or plasminogen activator inhibitor-1 (PAI-1)-deficient female mice. STZ treatment significantly decreased the numbers of F4/80-positive cells (macrophages), but not Gr-1-positive cells (neutrophils), at the damaged site on day 2 after femoral bone injury in mice...
March 8, 2018: Endocrinology
Olle Ringden, Arjang Baygan, Mats Remberger, Britt Gustafsson, Jacek Winiarski, Bita Khoein, Guido Moll, Lena Klingspor, Magnus Westgren, Behnam Sadeghi
Severe acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). The placenta protects the fetus from the mother's immune system. We evaluated placenta-derived decidua stromal cells (DSCs), which differ from bone marrow mesenchymal stromal cells (BM-MSCs), as a treatment for severe acute GVHD. DSCs were obtained from term placentas. The DSCs were given to 38 patients with severe acute GVHD; 25 were steroid refractory (SR). DSCs were thawed and infused in buffer supplemented with either 10% AB plasma (group 1, n = 17), or 5% albumin (group 2, n = 21)...
March 13, 2018: Stem Cells Translational Medicine
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