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Sepsis HSC

Débora Moreira Alvarenga, Matheus Silvério Mattos, Alan Moreira Araújo, Maísa Mota Antunes, Gustavo Batista Menezes
Neutrophils are the most abundant leukocyte in the human circulation. These short-lived cells are constantly produced from hematopoietic stem cells (HSC) within the bone marrow from which they daily reach the blood and perform major roles in innate immunity. Neutrophils are the first cells to reach inflamed tissues and are armed with a plethora of enzymes that help both with their trafficking within tissues and the killing of pathogens. Damaged or infected organs are rapidly invaded by neutrophils. Their erroneous activation within parenchyma or the vasculature is involved in the pathogenesis of several inflammatory diseases including arthritis, colitis, sepsis, acute lung injury and liver failure...
March 2018: Cell and Tissue Research
Ha-Yeun Chung, C Julius Witt, Nayla Jbeily, Jorge Hurtado-Oliveros, Benjamin Giszas, Amelie Lupp, Markus H Gräler, Tony Bruns, Andreas Stallmach, Falk A Gonnert, Ralf A Claus
The molecular mechanisms of maladaptive response in liver tissue with respect to the acute and post-acute phase of sepsis are not yet fully understood. Long-term sepsis survivors might develop hepatocellular/hepatobiliary injury and fibrosis. Here, we demonstrate that acid sphingomyelinase, an important regulator of hepatocyte apoptosis and hepatic stellate cell (HSC) activation, is linked to the promotion of liver dysfunction in the acute phase of sepsis as well as to fibrogenesis in the long-term. In both phases, we observed a beneficial effect of partial genetic sphingomyelinase deficiency in heterozygous animals (smpd1(+/-)) on oxidative stress levels, hepatobiliary function, macrophage infiltration and on HSC activation...
September 27, 2017: Scientific Reports
Kendra M Hodgkinson, Jeffrey Kiernan, Andrew W Shih, Ziad Solh, William P Sheffield, Nicolas Pineault
The principal theme of the symposium was centered on how the world of regenerative medicine intersects with that of transfusion medicine, with a particular focus on hematopoietic stem cells (HSCs) and stem cell therapies. The symposium highlighted several exciting developments and identified areas where additional research is needed. A revised map of human hematopoietic hierarchy was presented based on the functional and phenotypic analysis of thousands of single stem and progenitor cells from adult bone marrow and fetal liver...
July 2017: Transfusion Medicine Reviews
Huajia Zhang, Sonia Rodriguez, Lin Wang, Soujuan Wang, Henrique Serezani, Reuben Kapur, Angelo A Cardoso, Nadia Carlesso
Toll-like receptor 4 (TLR4) plays a central role in host responses to bacterial infection, but the precise mechanism(s) by which its downstream signaling components coordinate the bone marrow response to sepsis is poorly understood. Using mice deficient in TLR4 downstream adapters MYD88 or TRIF, we demonstrate that both cell-autonomous and non-cell-autonomous MYD88 activation are major causes of myelosuppression during sepsis, while having a modest impact on hematopoietic stem cell (HSC) functions. In contrast, cell-intrinsic TRIF activation severely compromises HSC self-renewal without directly affecting myeloid cells...
June 14, 2016: Stem Cell Reports
Alex G Cuenca, Angela L Cuenca, Lori F Gentile, Philip A Efron, Saleem Islam, Lyle L Moldawer, David W Kays, Shawn D Larson
Neonates have increased susceptibility to infection, which leads to increased mortality. Whether or not this as a result of implicit deficits in neonatal innate immune function or recapitulation of innate immune effector cell populations following infection is unknown. Here, we examine the process of emergency myelopoiesis whereby the host repopulates peripheral myeloid cells lost following the initial infectious insult. As early inflammatory responses are often dependent upon NF-κB and type I IFN signaling, we also examined whether the absence of MyD88, TRIF or MyD88 and TRIF signaling altered the myelopoietic response in neonates to polymicrobial sepsis...
May 2015: Innate Immunity
Bruce H Davis, Christine E McLaren, Anthony J Carcio, Linda Wong, Benjamin D Hedley, Mike Keeney, Adam Curtis, Naomi B Culp
Background: Assay validation includes determination of inherent imprecision across the reportable range. However specific practical guidelines for determinations of precision for cell based fluorescence assays performed on flow cytometers are currently lacking. Methods: Replicates of 10 or 20 measurements were obtained for flow cytometric assays developed for clinical IVD use, including neutrophil CD64 expression for infection/sepsis detection, fetal red cell enumeration for fetomaternal hemorrhage detection, human equilibrative nucleoside transporter 1 (hENT1) quantitation in leukocytes for possible correlation with drug responsiveness, and CD34+ hematopoietic stem cell (HSC) enumeration of apheresis products, using up to three different instrument platforms for each assay...
July 19, 2013: Cytometry. Part B, Clinical Cytometry
Joseph Leventhal, Michael Abecassis, Joshua Miller, Lorenzo Gallon, Kadiyala Ravindra, David J Tollerud, Bradley King, Mary Jane Elliott, Geoffrey Herzig, Roger Herzig, Suzanne T Ildstad
The toxicity of chronic immunosuppressive agents required for organ transplant maintenance has prompted investigators to pursue approaches to induce immune tolerance. We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSCs) and tolerogenic graft facilitating cells (FCs) combined with nonmyeloablative conditioning; this approach resulted in engraftment, durable chimerism, and tolerance induction in recipients with highly mismatched related and unrelated donors...
March 7, 2012: Science Translational Medicine
Stefan Stein, Marion G Ott, Stephan Schultze-Strasser, Anna Jauch, Barbara Burwinkel, Andrea Kinner, Manfred Schmidt, Alwin Krämer, Joachim Schwäble, Hanno Glimm, Ulrike Koehl, Carolin Preiss, Claudia Ball, Hans Martin, Gudrun Göhring, Kerstin Schwarzwaelder, Wolf-Karsten Hofmann, Kadin Karakaya, Sandrine Tchatchou, Rongxi Yang, Petra Reinecke, Klaus Kühlcke, Brigitte Schlegelberger, Adrian J Thrasher, Dieter Hoelzer, Reinhard Seger, Christof von Kalle, Manuel Grez
Gene-modified autologous hematopoietic stem cells (HSC) can provide ample clinical benefits to subjects suffering from X-linked chronic granulomatous disease (X-CGD), a rare inherited immunodeficiency characterized by recurrent, often life-threatening bacterial and fungal infections. Here we report on the molecular and cellular events observed in two young adults with X-CGD treated by gene therapy in 2004. After the initial resolution of bacterial and fungal infections, both subjects showed silencing of transgene expression due to methylation of the viral promoter, and myelodysplasia with monosomy 7 as a result of insertional activation of ecotropic viral integration site 1 (EVI1)...
February 2010: Nature Medicine
Sonia Rodriguez, Angelo Chora, Boyan Goumnerov, Christen Mumaw, W Scott Goebel, Luis Fernandez, Hasan Baydoun, Harm HogenEsch, David M Dombkowski, Carol A Karlewicz, Susan Rice, Laurence G Rahme, Nadia Carlesso
Severe sepsis is one of the leading causes of death worldwide. High mortality rates in sepsis are frequently associated with neutropenia. Despite the central role of neutrophils in innate immunity, the mechanisms causing neutropenia during sepsis remain elusive. Here, we show that neutropenia is caused in part by apoptosis and is sustained by a block of hematopoietic stem cell (HSC) differentiation. Using a sepsis murine model, we found that the human opportunistic bacterial pathogen Pseudomonas aeruginosa caused neutrophil depletion and expansion of the HSC pool in the bone marrow...
November 5, 2009: Blood
Jennifer G Hall, Joanne Kurtzberg, Paul Szabolcs, Michael A Skinner, Henry E Rice
UNLABELLED: Hematopoietic stem cell (HSC) engraftment is delayed in children with hypersplenism, and splenectomy may improve HSC engraftment. However, the use of total splenectomy in children is limited because of concerns for postsplenectomy sepsis. In this study, the authors sought to assess the role of partial splenectomy for children with hypersplenism undergoing HSC transplantation. METHODS: Five children with a variety of conditions and associated hypersplenism underwent partial splenectomy before an HSC transplantation at the authors' institution between 2000 and 2003...
January 2005: Journal of Pediatric Surgery
S M Devine, R Sanborn, E Jessop, W Stock, M Huml, D Peace, A Wickrema, M Yassine, K Amin, D Thomason, Y H Chen, H Devine, M Maningo, K van Besien
Severe regimen-related toxicity often complicates second transplant procedures performed in patients with hematological malignancies that have relapsed after an initial hematopoietic stem cell (HSC) transplant. Therefore, we studied the safety and efficacy of a reduced-intensity fludarabine and melphalan based conditioning regimen in 11 patients who had relapsed following an autologous (n = 7) or allogeneic (n = 4) HSC transplant. All patients received allogeneic peripheral blood HSC from either an HLA-identical (n = 7) or an HLA-mismatched (n = 4) relative...
September 2001: Bone Marrow Transplantation
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