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https://www.readbyqxmd.com/read/29150659/ectopic-foxp3-expression-preserves-primitive-features-of-human-hematopoietic-stem-cells-while-impairing-functional-t-cell-differentiation
#1
F R Santoni de Sio, L Passerini, M M Valente, F Russo, L Naldini, M G Roncarolo, R Bacchetta
FOXP3 is the transcription factor ruling regulatory T cell function and maintenance of peripheral immune tolerance, and mutations in its coding gene causes IPEX autoimmune syndrome. FOXP3 is also a cell-cycle inhibitor and onco-suppressor in different cell types. In this work, we investigate the effect of ectopic FOXP3 expression on HSC differentiation and we challenged this approach as a possible HSC-based gene therapy for IPEX. FOXP3-expressing HSC showed reduced proliferation ability and increased maintenance of primitive markers in vitro in both liquid and OP9-ΔL1 co-cultures...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29149103/human-hepatocyte-transplantation-for-liver-disease-current-status-and-future-perspectives
#2
REVIEW
Valeria Iansante, Ragai R Mitry, Céline Filippi, Emer Fitzpatrick, Anil Dhawan
Liver transplantation is the accepted treatment for patients with acute liver failure and liver-based metabolic disorders. However, donor organ shortage and lifelong need for immunosuppression are the main limitations to liver transplantation. In addition, loss of the native liver as target organ for future gene therapy for metabolic disorders limits the futuristic treatment options, resulting in the need for alternative therapeutic strategies. A potential alternative to liver transplantation is allogeneic hepatocyte transplantation...
November 14, 2017: Pediatric Research
https://www.readbyqxmd.com/read/29147721/osteomimicry-how-the-seed-grows-in-the-soil
#3
REVIEW
Nadia Rucci, Anna Teti
Metastasis is defined as a very inefficient process, since less than 0.01% of cancer cells injected into the circulation will engraft in a distant organ, where they must acquire the ability to survive and proliferate inside a "foreign" environment. In bone metastases, the interaction with the host organ is much more favoured if tumour cells gain "osteomimicry", that is the ability to resemble a resident bone cell (i.e. the osteoblast), thus intruding in the physiology of the bone. This is accomplished by the expression of osteoblast markers (e...
November 16, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29147625/a-transcriptomic-insight-into-the-impacts-of-mast-cells-in-lung-breast-and-colon-cancers
#4
Eun-A Ko, Kenton M Sanders, Tong Zhou
To date, the exact impact of mast cells in tumor microenvironment is still controversial because of inconsistency in observations regarding the relationship between mast cell infiltrates and cancer development and prognosis. The discrepancies in previous studies have motivated us to examine the roles of mast cells in cancer pathology from different perspectives. Here, we investigated the impact of mast cells on transcriptomic profiles in the tissue microenvironment. Mice carrying the W-sh mutation in c-kit (Kit(W-sh) ) are deficient in mast cell production and were used to assess the influence of mast cells on gene expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146734/humanized-mice-in-studying-efficacy-and-mechanisms-of-pd-1-targeted-cancer-immunotherapy
#5
Minan Wang, Li-Chin Yao, Mingshan Cheng, Danying Cai, Jan Martinek, Chong-Xian Pan, Wei Shi, Ai-Hong Ma, Ralph W De Vere White, Susan Airhart, Edison T Liu, Jacques Banchereau, Michael A Brehm, Dale L Greiner, Leonard D Shultz, Karolina Palucka, James G Keck
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, non-obese diabetic (NOD).Cg-Prkdc(scid)IL2rg(tm1Wjl) /Sz (null; NSG) mice were transplanted with human (h)CD34(+) hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; nonsmall cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146574/mast-cell-dependent-il-33-st2-signaling-is-protective-against-the-development-of-airway-hyperresponsiveness-in-a-house-dust-mite-mouse-model-of-asthma
#6
Anna Maria Zoltowska Nilsson, Ying Lei, Mikael Adner, Gunnar P Nilsson
Interleukin-33 (IL-33) and its receptor ST2 have been influentially associated to the pathophysiology of asthma. Due to the divergent roles of IL-33 in regulating mast cell functions, there is a need to further characterize IL-33/ST2-dependent mast cell responses and their significance in the context of asthma. This study aimed to investigate how IL-33/ST2-dependent mast cell responses contribute to the development of airway hyperresponsiveness (AHR) and airway inflammation in a mouse model of house dust mite (HDM) induced asthma...
November 16, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29143337/intraductal-papillary-mucinous-neoplasm-of-the-pancreas-rapidly-xenografts-in-chicken-eggs-and-predicts-aggressiveness
#7
Zhefu Zhao, Nathalie Bauer, Ewa Aleksandrowicz, Libo Yin, Jury Gladkich, Wolfgang Gross, Jörg Kaiser, Thilo Hackert, Oliver Strobel, Ingrid Herr
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has a high risk of progressing to invasive pancreatic ductal adenocarcinoma (PDA), but experimental models for IPMN are largely missing. New experimental systems for the molecular characterization of IPMN and for personalized prognosis and treatment options for IPMN are urgently needed. We analyzed the potential use of fertilized chicken eggs for the culture of freshly resected IPMN tissue. We transplanted 49 freshly resected IPMN tissues into eggs and compared the growth characteristics to IPMN tissues transplanted into mice; this was followed by an analysis of histology, morphology and marker expression...
November 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29141507/sandwiched-white-adipose-tissue-a-novel-microphysiological-system-of-human-adipose-tissue
#8
Frank H Lau, Kelly Vogel, John P Luckett, Maxwell Hunt, Alicia Meyer, Camille L Rogers, Oren Tessler, Charles L Dupin, Hugo St Hilaire, Kazi N Islam, Trivia Frazier, Jeffrey Gimble, Steven Scahill
White adipose tissue (WAT) is a critical organ in both health and disease. However, physiologically faithful tissue culture models of primary human WAT remain limited, at best. Here we describe a novel WAT culture system in which primary human WAT is sandwiched between tissue-engineered sheets of adipose-derived stromal cells. This construct, called "sandwiched white adipose tissue" (SWAT), can be defined as a Microphysiological System (MPS) since it is a tissue-engineered, multicellular, 3D organ construct produced using human cells...
November 16, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/29140566/mesenchymal-stem-cell-preparation-and-transfection-free-ferumoxytol-labeling-for-mri-cell-tracking
#9
Li Liu, Chien Ho
Mesenchymal stem cells (MSCs) are multipotent cells and are the most widely studied cell type for stem cell therapies. In vivo cell tracking of MSCs labeled with an FDA-approved superparamagnetic iron-oxide (SPIO) particle by magnetic resonance imaging (MRI) provides essential information, e.g., MSC engraftment, survival, and fate, thus improving cell therapy accuracy. However, current methodology for labeling MSCs with Ferumoxytol (Feraheme(®) ), the only FDA-approved SPIO particle, needs transfection agents...
November 15, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/29137845/enumeration-of-bone-marrow-plasmacytoid-dendritic-cells-by-multiparameter-flow-cytometry-as-a-prognostic-marker-following-allogeneic-hematopoietic-stem-cell-transplantation
#10
Ruijun Jeanna Su, Ralph Green, Mingyi Chen
Plasmacytoid dendritic cells (pDCs) promote tolerance in solid organ transplants and hematopoietic stem cell transplantation (HSCT). pDCs originate from CD34(+) hematopoietic progenitors. Following allogeneic hematopoietic stem cell transplant (allo-HSCT), pDC reconstitution in the BM and PB gradually attain levels similar to those in healthy individuals. We have investigated the recovery of pDC following allo-HSCT as a means to predict successful marrow engraftment. We retrospectively studied immune reconstitution of pDC in the BM of 48 patients following allo-HSCT for initial diagnoses of leukemia or other malignancies...
October 31, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29137385/improved-outcome-of-haploidentical-transplantation-in-severe-aplastic-anemia-using-reduced-intensity-fludarabine-based-conditioning
#11
Wu Yamei, Luo Rongmu, Cao Yongbin, Si Yingjian, Li Xiaohong, Zhang Xiaomei, Yan Pei, Du Zhenlan, Wang Haitao, Wang Jing, Wang Bojing, Wu Xiaoxiong, Da Wanming
Significant improvements in hematopoietic stem cell transplantation (HSCT) with haploidentical family donors (HFD) have confirmed its therapeutic role in severe aplastic anemia (SAA) and led to the evolution of treatment algorithms. However, the optimal conditioning regimen for HFD-HSCT remains undefined, especially the dosage of cyclophosphamide (Cy). A total of 77 patients with SAA from two research centers, who received HFD-HSCT with reduced-intensity fludarabine + cyclophosphamide + thymoglobulin ± busulfan conditioning regimen plus third-party cells infusion were included in this study, of which 67 pairs had 4-5 loci mismatched...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137234/the-af4-mll-fusion-transiently-augments-multilineage-hematopoietic-engraftment-but-is-not-sufficient-to-initiate-leukemia-in-cord-blood-cd34-cells
#12
Cristina Prieto, Rolf Marschalek, Alessa Kühn, Adelheid Bursen, Clara Bueno, Pablo Menéndez
The translocation t(4;11)(q21;q23) is the hallmark genetic abnormality associated with infant pro-B acute lymphoblastic leukemia (B-ALL) and has the highest frequency of rearrangement in Mixed-lineage leukemia (MLL) leukemias. Unlike other MLL translocations, MLL-AF4-induced proB-ALL is exceptionally difficult to model in mice/humans. Previous work has investigated the relevance of the reciprocal translocation fusion protein AF4-MLL for t(4;11) leukemia, finding that AF4-MLL is capable of inducing proB-ALL without requirement for MLL-AF4 when expressed in murine hematopoietic stem/progenitor cells (HSPCs)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29132800/fetal-bone-marrow-homing-of-donor-mesenchymal-stem-cells-after-transamniotic-stem-cell-therapy-trascet
#13
Hester F Shieh, Azra Ahmed, Sarah A Tracy, David Zurakowski, Dario O Fauza
PURPOSE: Donor cell engraftment patterns following transamniotic stem cell therapy (TRASCET) with amniotic fluid mesenchymal stem cells (afMSCs) are incompatible with solely direct amniotic seeding. We sought to determine whether fetal bone marrow is a component of such engraftment and to examine the chronology of afMSC placental trafficking. METHODS: Two groups of Sprague-Dawley rat fetuses received volume-matched intraamniotic injections on gestational day 17 (E17; term E22): either afMSCs labeled with a luciferase reporter gene or luciferase protein alone...
October 12, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29132746/diabetes-mellitus-as-a-poor-mobilizer-condition
#14
REVIEW
Gian Paolo Fadini, John F DiPersio
Hematopoietic stem cell (HSC) transplantation in an effective and curative therapy for numerous hematological malignancies. Mobilization of HSCs from bone marrow (BM) to peripheral blood (PB) followed by apheresis is the gold standard for obtaining HSCs for both autologous and allogeneic stem cell transplantation. After administration of granulocyte-colony stimulating factor (G-CSF), up to 30% of patients fail to mobilize "optimal" numbers of HSCs required for engraftment. This review summarizes the current experimental and clinical evidence that diabetes mellitus is a risk factor for poor mobilization...
November 8, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29131150/neurologic-complications-after-allogeneic-hematopoietic-stem-cell-transplantation-risk-factors-and-impact
#15
M R Dowling, S Li, B R Dey, S L McAfee, H R Hock, T R Spitzer, Y-B Chen, K K Ballen
Neurologic complications (NCs) may be a significant source of morbidity and mortality after hematopoietic cell transplantation (HCT). We performed a retrospective study of 263 consecutive patients undergoing allogeneic HCT for hematological malignancies to determine the incidence, risk factors and clinical impact of NCs in the first 5 years after HCT. We determined the incidence of central nervous system (CNS) infection, intracranial hemorrhage, ischemic stroke, metabolic encephalopathy, posterior reversal encephalopathy syndrome, seizure and peripheral neuropathy...
November 13, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29129708/efficacy-of-hepatitis-b-virus-ribonuclease-h-inhibitors-a-new-class-of-replication-antagonists-in-frg-human-liver-chimeric-mice
#16
Kelly R Long, Elena Lomonosova, Qilan Li, Nathan L Ponzar, Juan A Villa, Erin Touchette, Stephen Rapp, R Matt Liley, Ryan P Murelli, Alexandre Grigoryan, R Mark Buller, Lisa Wilson, John Bial, John E Sagartz, John E Tavis
Chronic hepatitis B virus infection cannot be cured by current therapies, so new treatments are urgently needed. We recently identified novel inhibitors of the hepatitis B virus ribonuclease H that suppress viral replication in cell culture. Here, we employed immunodeficient FRG KO mice whose livers had been engrafted with primary human hepatocytes to ask whether ribonuclease H inhibitors can suppress hepatitis B virus replication in vivo. Humanized FRG KO mice infected with hepatitis B virus were treated for two weeks with the ribonuclease H inhibitors #110, an α-hydroxytropolone, and #208, an N-hydroxypyridinedione...
November 9, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29128556/pro-140-monoclonal-antibody-to-ccr5-prevents-acute-xenogeneic-graft-versus-host-disease-in-nod-scid-il-2ry-null-mice
#17
Denis R Burger, Yvonne Parker, Kathryn Guinta, Daniel Lindner
Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication of hematopoietic stem cell transplantation (HSCT). Humanized mouse models of xenogeneic-GvHD are important tools used to study the human immune response in vivo. Here we used NOD-scid IL-2Ry(null) mice (NSG) transplanted with human bone marrow stem cells to evaluate the role of immune cell engraftment in the production of acute GvHD. PRO 140, a humanized monoclonal antibody targeting the chemokine receptor, CCR5, was used to evaluate its influence on bone marrow cell engraftment and modulation of acute GvHD...
November 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29128555/combined-haploidentical-and-umbilical-cord-blood-allogeneic-stem-cell-transplantation-for-high-risk-lymphoma-and-cll
#18
Jingmei Hsu, Andrew Artz, Sebastian A Mayer, Danielle Guarner, Michael R Bishop, Ronit Reich-Slotky, Sonali M Smith, June Greenberg, Justin Kline, Rosanna Ferrante, Adrienne A Phillips, Usama Gergis, Hongtao Liu, Wendy Stock, Melissa Cushing, Tsiporah B Shore, Koen van Besien
Limited studies have reported on outcomes for lymphoid malignancy patients receiving alternative donor allogeneic stem cell transplants. We have previously described combining CD34-selected haploidentical grafts with umbilical cord blood (haplo-cord) to accelerate neutrophil and platelet engraftment. Here, we examine the outcome of patients with lymphoid malignancies undergoing haplo-cord transplantation at the University of Chicago and Weill Cornell Medical College. We analyzed 42 lymphoma and CLL patients who underwent haplo-cord allogeneic stem cell transplantation...
November 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29128084/-chimerism-analysis-after-hematopoietic-cell-transplantation-guidelines-from-the-francophone-society-of-bone-marrow-transplantation-and-cellular-therapy-sfgm-tc
#19
Valérie Dubois, Mehdi Alizadeh, Jean Henri Bourhis, Pascaline Etancelin, Olivier Farchi, Christophe Ferrand, Laure Goursaud, Isabelle Mollet, Virginie Renac, Pauline Varlet, Ibrahim Yakoub-Agha, Jacques-Olivier Bay
Chimerism analysis is an important step for the patient follow-up after hematopoietic stem cell transplantation. It is used to quantify the donor and the recipient part of a cell population issued from blood or bone marrow sample. In addition to hemogram, this technique is necessary to appreciate the quality of engraftment. The aim of this article is to propose some recommendation about methods, result analysis and therapeutic decision in hematopoietic stem cell transplantation for malignant or non-malignant diseases...
November 8, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29127679/alternative-donor-unrelated-donor-transplants-for-the-%C3%AE-thalassemia-and-sickle-cell-disease
#20
Courtney D Fitzhugh, Allistair Abraham, Matthew M Hsieh
Considerable progress with respect to donor source has been achieved in allogeneic stem cell transplant for patients with hemoglobin disorders, with matched sibling donors in the 1980s, matched unrelated donors and cord blood sources in the 1990s, and haploidentical donors in the 2000s. Many studies have solidified hematopoietic progenitors from matched sibling marrow, cord blood, or mobilized peripheral blood as the best source-with the lowest graft rejection and graft versus host disease (GvHD), and highest disease-free survival rates...
2017: Advances in Experimental Medicine and Biology
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