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Bone marrow engraftment

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https://www.readbyqxmd.com/read/28636844/clonal-hematopoiesis-and-risk-of-atherosclerotic-cardiovascular-disease
#1
Siddhartha Jaiswal, Pradeep Natarajan, Alexander J Silver, Christopher J Gibson, Alexander G Bick, Eugenia Shvartz, Marie McConkey, Namrata Gupta, Stacey Gabriel, Diego Ardissino, Usman Baber, Roxana Mehran, Valentin Fuster, John Danesh, Philippe Frossard, Danish Saleheen, Olle Melander, Galina K Sukhova, Donna Neuberg, Peter Libby, Sekar Kathiresan, Benjamin L Ebert
Background Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among older persons and is associated with an increased risk of hematologic cancer. We previously found preliminary evidence for an association between CHIP and atherosclerotic cardiovascular disease, but the nature of this association was unclear. Methods We used whole-exome sequencing to detect the presence of CHIP in peripheral-blood cells and associated such presence with coronary heart disease using samples from four case-control studies that together enrolled 4726 participants with coronary heart disease and 3529 controls...
June 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28634334/image-guided-transplantation-of-single-cells-in-the-bone-marrow-of-live-animals
#2
Raphaël Turcotte, Clemens Alt, Judith M Runnels, Kyoko Ito, Juwell W Wu, Walid Zaher, Luke J Mortensen, Lev Silberstein, Daniel C Côté, Andrew L Kung, Keisuke Ito, Charles P Lin
Transplantation of a single hematopoietic stem cell is an important method for its functional characterization, but the standard transplantation protocol relies on cell homing to the bone marrow after intravenous injection. Here, we present a method to transplant single cells directly into the bone marrow of live mice. We developed an optical platform that integrates a multiphoton microscope with a laser ablation unit for microsurgery and an optical tweezer for cell micromanipulation. These tools allow image-guided single cell transplantation with high spatial control...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28626778/single-cell-based-vector-tracing-in-patients-with-ada-scid-treated-with-stem-cell-gene-therapy
#3
Yuka Igarashi, Toru Uchiyama, Tomoko Minegishi, Sirirat Takahashi, Nobuyuki Watanabe, Toshinao Kawai, Masafumi Yamada, Tadashi Ariga, Masafumi Onodera
Clinical improvement in stem cell gene therapy (SCGT) for primary immunodeficiencies depends on the engraftment levels of genetically corrected cells, and tracing the transgene in each hematopoietic lineage is therefore extremely important in evaluating the efficacy of SCGT. We established a single cell-based droplet digital PCR (sc-ddPCR) method consisting of the encapsulation of a single cell into each droplet, followed by emulsion PCR with primers and probes specific for the transgene. A fluorescent signal in a droplet indicates the presence of a single cell carrying the target gene in its genome, and this system can clearly determine the ratio of transgene-positive cells in the entire population at the genomic level...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28623394/disease-specific-hematopoietic-stem-cell-transplantation-in-children-with-inherited-bone-marrow-failure-syndromes
#4
Qian Li, Changying Luo, Chengjuan Luo, Jianmin Wang, Benshang Li, Lixia Ding, Jing Chen
Hematopoietic stem cell transplantation (HSCT) using an optimized conditioning regimen is essential for the long-term survival of patients with inherited bone marrow failure syndromes (IBMFS). We report HSCT in 24 children with Fanconi anemia (FA, n = 12), Diamond-Blackfan anemia (DBA, n = 7), and dyskeratosis congenita (DC, n = 5) from a single HSCT center. The graft source was peripheral blood stem cells (n = 19) or cord blood stem cells (n = 5). FA and DC patients received reduced-intensity conditioning, while DBA patients had myeloablative conditioning...
August 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28607915/engineering-cord-blood-to-improve-engraftment-after-cord-blood-transplant
#5
REVIEW
Rohtesh S Mehta, Hema Dave, Catherine M Bollard, Elizabeth J Shpall
Umbilical cord blood transplant (CBT) has traditionally been associated with slower engraftment of neutrophils, delayed immune reconstitution and consequently higher risk of infections as compared with peripheral blood progenitor cell (PBPC) or bone marrow (BM) transplants. This is primarily due to low numbers of total nucleated cells (TNCs) and the naive nature of CB immune cells. The use of double unit CB transplant (DCBT) increases the total cell dose in the graft, but it still does not produce as rapid engraftment as seen with PBPC or even BM transplants...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28603070/clinical-utility-of-quantitative-pcr-for-chimerism-and-engraftment-monitoring-after-allogeneic-stem-cell-transplantation-for-hematologic-malignancies
#6
Müberra Ahci, Karin Stempelmann, Ulrike Buttkereit, Pietro Crivello, Mirko Trilling, Andreas Heinold, Nina Kristin Steckel, Michael Koldehoff, Peter A Horn, Dietrich W Beelen, Katharina Fleischhauer
Although quantitative PCR (qPCR) has been explored for chimerism monitoring after allogeneic stem cell transplantation (SCT), evidence regarding its clinical utility compared to standard short tandem repeat (STR) is still limited. We retrospectively studied commercial qPCR and STR chimerism with respective positivity thresholds of 0.1% and 1%, in 359 peripheral blood (PB) and 95 bone marrow (BM) samples from 30 adult patients after first HLA-matched SCT for myeloid malignancies or acute lymphatic leukemia. Concordance between the two methods was 79...
June 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28599679/evaluation-of-bone-marrow-mononuclear-cells-as-an-adjunct-therapy-to-minced-muscle-graft-for-the-treatment-of-volumetric-muscle-loss-injuries
#7
Stephen M Goldman, Beth E P Henderson, Benjamin T Corona
BACKGROUND: The delivery of alternative myogenic cell sources to enhance the efficacy of minced muscle grafts (MG) for the treatment of volumetric muscle loss (VML) injuries is a promising strategy to overcome the demand on muscle-derived donor tissue that currently limits the translation of this therapy. METHODS: Using a rat model of VML, bone marrow mononuclear cells (BMNCs) were evaluated for their ability to directly contribute to de novo muscle fiber regeneration by transplanting MG in a collagen carrier at a dose of 50% of the VML injury both with and without concomitant delivery of 5 million BMNCs derived via density gradient centrifugation from the bone marrow of a syngeneic green fluorescent protein (GFP)(+) donor...
June 9, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28596651/bacteremia-during-early-post-allogeneic-hematopoietic-stem-cell-transplantation-period-a-single-center-experience
#8
Amro Mohamed Sedky El-Ghammaz
Bacteremia is a significant complication of allogeneic hematopoietic stem cell transplantation (HSCT). We aimed to study bacteremia occurring during early post-transplant period at Bone Marrow Transplantation Unit of Ain Shams University regarding its risk factors and impact on survival. Patients performing allogeneic HSCT were followed up for occurrence of bacteremia. Survival status was assessed at 180 days post-transplant. Bacteremia occurred in 53.3 % of patients. On univariate analysis, CD34 +ve cell dose (P = 0...
June 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28585336/liver-directed-human-amniotic-epithelial-cell-transplantation-improves-systemic-disease-phenotype-in-hurler-syndrome-mouse-model
#9
Natalie S Rodriguez, Lisa Yanuaria, Kevin Murphy R Parducho, Irving M Garcia, Bino A Varghese, Brendan H Grubbs, Toshio Miki
Mucopolysaccharidosis type 1 (MPS1) is an inherited lysosomal storage disorder caused by a deficiency in the glycosaminoglycan (GAG)-degrading enzyme α-l-iduronidase (IDUA). In affected patients, the systemic accumulation of GAGs results in skeletal dysplasia, neurological degeneration, multiple organ dysfunction, and early death. Current therapies, including enzyme replacement and bone marrow transplant, improve life expectancy but the benefits to skeletal and neurological phenotypes are limited. In this study, we tested the therapeutic efficacy of liver-directed transplantation of a placental stem cell, which possesses multilineage differentiation potential, low immunogenicity, and high lysosomal enzyme activity...
June 6, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28576879/robust-patient-derived-xenografts-of-mds-mpn-overlap-syndromes-capture-the-unique-characteristics-of-cmml-and-jmml
#10
Akihide Yoshimi, Maria E Balasis, Alexis Vedder, Kira Feldman, Yan Ma, Hailing Zhang, Stanley Chun-Wei Lee, Christopher Letson, Sandrine Niyongere, Sydney X Lu, Markus Ball, Justin Taylor, Qing Zhang, Yulong Zhao, Salma Youssef, Young Rock Chung, Xiao Jing Zhang, Benjamin H Durham, Wendy Yang, Alan F List, Mignon L Loh, Virginia Klimek, Michael F Berger, Elliot Stieglitz, Eric Padron, Omar Abdel-Wahab
Chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML) are characterized by monocytosis, myelodysplasia, and a characteristic hypersensitivity to GM-CSF. Currently, there are no available disease-modifying therapies for CMML, nor are there preclinical models that fully recapitulate the unique features of CMML. Through use of immunocompromised mice with transgenic expression of human GM-CSF, IL-3, and SCF in a NOD/SCID-IL2Rγ(null) background (NSGS mice), we demonstrate remarkable engraftment of CMML and JMML providing the first examples of serially transplantable and genetically accurate models of CMML...
June 2, 2017: Blood
https://www.readbyqxmd.com/read/28573314/reduced-toxicity-myeloablative-hla-haploidentical-hematopoietic-stem-cell-transplantation-with-post-transplantation-cyclophosphamide-for-sickle-cell-disease
#11
Volker Wiebking, Sebastian Hütker, Irene Schmid, Stefanie Immler, Tobias Feuchtinger, Michael H Albert
Allogeneic hematopoietic stem cell transplantation (HSCT) offers the possibility of cure for sickle cell disease (SCD) patients. Unfortunately, the probability of finding an HLA-matched donor for SCD patients is low. HSCT from HLA-haploidentical donors using reduced intensity conditioning, unmanipulated bone marrow and post-transplantation cyclophosphamide (ptCy) has resulted in negligible toxicity but high rates of graft rejection. We hypothesized that combining ptCy with a myeloablative reduced toxicity conditioning including serotherapy to increase immune ablation would allow for better engraftment...
June 1, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28573310/inhibition-of-neuropathic-hyperalgesia-by-intrathecal-bone-marrow-stromal-cells-is-associated-with-alteration-of-multiple-soluble-factors-in-cerebrospinal-fluid
#12
Gregory Fischer, Fei Wang, Hongfei Xiang, Xiaowen Bai, Hongwei Yu, Quinn H Hogan
Injury-induced neuropathic pain remains a serious clinical problem. Recent studies indicate that bone marrow stromal cells (BMSCs) effectively attenuate chronic neuropathic pain in animal models. Here, we examined the therapeutic effect of intrathecal administration of BMSCs isolated from young (1-month-old) rats on pain hypersensitivity induced by tibial nerve injury. Cerebrospinal fluid (CSF) was collected and analyzed to examine the effect of BMSC administration on the expression of 67 soluble factors in CSF...
June 1, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28570944/oral-feeding-with-polyunsaturated-fatty-acids-fosters-hematopoiesis-and-thrombopoiesis-in-healthy-and-bone-marrow-transplanted-mice
#13
Kedar Limbkar, Ankita Dhenge, Dipesh D Jadhav, Hirekodathakallu V Thulasiram, Vaijayanti Kale, Lalita Limaye
Hematopoietic stem cells play the vital role of maintaining appropriate levels of cells in blood. Therefore, regulation of their fate is essential for their effective therapeutic use. Here we report the role of polyunsaturated fatty acids (PUFAs) in regulating hematopoiesis which has not been explored well so far. Mice were fed daily for 10 days with n-6/n-3 PUFAs, viz. linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid and docosahexanoic acid (DHA) in four separate test groups with phosphate-buffered saline fed mice as control set...
May 17, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28558762/unmanipulated-haploidentical-stem-cell-transplantation-in-adults-with-acute-lymphoblastic-leukemia-a-study-on-behalf-of-the-acute-leukemia-working-party-of-the-ebmt
#14
Nicole Santoro, Annalisa Ruggeri, Myriam Labopin, Andrea Bacigalupo, Fabio Ciceri, Zafer Gülbaş, He Huang, Boris Afanasyev, William Arcese, Depei Wu, Yener Koc, Johanna Tischer, Stella Santarone, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
BACKGROUND: Allogenic hematopoietic stem cell transplantation (allo-SCT) is the most effective post-remission treatment for adults with high-risk acute lymphoblastic leukemia (ALL). The aim of the study was to analyze results of unmanipulated haploidentical allo-SCT (haplo-SCT) for adults with ALL and to identify prognostic factors. METHODS: We performed a retrospective analysis on 208 adults transplanted in EBMT centers from 2007 to 2014. RESULTS: Median age at haplo-SCT was 32 years and median follow-up, 31 months...
May 30, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28539439/contribution-of-human-lung-parenchyma-and-leukocyte-influx-to-oxidative-stress-and-immune-mediated-pathology-following-nipah-infection
#15
Olivier Escaffre, Tais B Saito, Terry L Juelich, Tetsuro Ikegami, Jennifer K Smith, David D Perez, Colm Atkins, Corri B Levine, Matthew B Huante, Rebecca J Nusbaum, Janice J Endsley, Alexander N Freiberg, Barry Rockx
Nipah virus (NiV) is a zoonotic emerging paramyxovirus that can cause a fatal respiratory illness or encephalitis in humans. Despite many efforts, the molecular mechanisms of NiV-induced acute lung injury (ALI) remain unclear. We previously showed that NiV replicates to high titers in human lung grafts in NOD scid gamma mice, resulting in a robust inflammatory response. Interestingly, these mice can undergo human immune system reconstitution by the Bone marrow, Liver, and Thymus (BLT) reconstitution method, in addition to lung tissue engraftment, giving altogether a realistic model to study human respiratory viral infections...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28533307/sox11-promotes-tumor-protective-microenvironment-interactions-through-cxcr4-and-fak-regulation-in-mantle-cell-lymphoma
#16
Patricia Balsas, Jara Palomero, Álvaro Eguileor, Marta Leonor Rodriguez, Maria Carmela Vegliante, Ester Planas-Rigol, Marta Sureda-Gómez, Maria C Cid, Elias Campo, Virginia Amador
SOX11 overexpression in Mantle Cell Lymphoma (MCL) has been associated with more aggresive behavior and worse outcome. However, SOX11 oncogenic pathways driving MCL tumor progression are poorly known. Here, we demonstrate that SOX11 binds to regulatory regions of two important genes for microenvironment-signals in cancer, (C-X-C motif) chemokine receptor 4 (CXCR4) and PTK2 (encoding for focal adhesion kinase (FAK)). Moreover, SOX11-positive xenograft and human primary MCL tumors overexpress cell migration and stromal stimulation gene signatures compared to their SOX11-negative counterparts...
May 22, 2017: Blood
https://www.readbyqxmd.com/read/28512561/bone-marrow-homing-and-engraftment-defects-of-human-hematopoietic-stem-and-progenitor-cells
#17
REVIEW
Giovanni Caocci, Marianna Greco, Giorgio La Nasa
Homing of hematopoietic stem cells (HSC) to their microenvironment niches in the bone marrow is a complex process with a critical role in repopulation of the bone marrow after transplantation. This active process allows for migration of HSC from peripheral blood and their successful anchoring in bone marrow before proliferation. The process of engraftment starts with the onset of proliferation and must, therefore, be functionally dissociated from the former process. In this overview, we analyze the characteristics of stem cells (SCs) with particular emphasis on their plasticity and ability to find their way home to the bone marrow...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28507545/clinical-and-molecular-heterogeneity-of-rtel1-deficiency
#18
Carsten Speckmann, Sushree Sangita Sahoo, Marta Rizzi, Shinsuke Hirabayashi, Axel Karow, Nina Kathrin Serwas, Marc Hoemberg, Natalja Damatova, Detlev Schindler, Jean-Baptiste Vannier, Simon J Boulton, Ulrich Pannicke, Gudrun Göhring, Kathrin Thomay, J J Verdu-Amoros, Holger Hauch, Wilhelm Woessmann, Gabriele Escherich, Eckart Laack, Liliana Rindle, Maximilian Seidl, Anne Rensing-Ehl, Ekkehart Lausch, Christine Jandrasits, Brigitte Strahm, Klaus Schwarz, Stephan R Ehl, Charlotte Niemeyer, Kaan Boztug, Marcin W Wlodarski
Typical features of dyskeratosis congenita (DC) resulting from excessive telomere shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized. We report our observations in a cohort of six patients: five with novel biallelic RTEL1 mutations p...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28501622/the-role-of-plasmin-in-the-pathogenesis-of-murine-multiple-myeloma
#19
Salita Eiamboonsert, Yousef Salama, Hiroshi Watarai, Douaa Dhahri, Yuko Tsuda, Yoshio Okada, Koichi Hattori, Beate Heissig
Aside from a role in clot dissolution, the fibrinolytic factor, plasmin is implicated in tumorigenesis. Although abnormalities of coagulation and fibrinolysis have been reported in multiple myeloma patients, the biological roles of fibrinolytic factors in multiple myeloma (MM) using in vivo models have not been elucidated. In this study, we established a murine model of fulminant MM with bone marrow and extramedullar engraftment after intravenous injection of B53 cells. We found that the fibrinolytic factor expression pattern in murine B53 MM cells is similar to the expression pattern reported in primary human MM cells...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28499937/haploidentical-allogeneic-hematopoietic-cell-transplantation-for-multiple-myeloma-using-post-transplantation-cyclophosphamide-graft-versus-host-disease-prophylaxis
#20
Luca Castagna, Alberto Mussetti, Raynier Devillier, Alida Dominietto, Magda Marcatti, Giuseppe Milone, Francesco Maura, Chiara de Philippis, Benedetto Bruno, Sabine Furst, Didier Blaise, Paolo Corradini, Vittorio Montefusco
Allogeneic (allo) hematopoietic cell transplantation (HCT) currently represents the only potentially curative therapy for patients affected by multiple myeloma (MM). Up to 30% of patients in western countries do not have a matched donor. Haploidentical HCT (haplo-HCT) may be an option, but currently, there are little available data regarding this treatment. We analyzed survival outcomes of 30 heavily pretreated MM patients who received haplo-HCT with post-transplantation cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis...
May 10, 2017: Biology of Blood and Marrow Transplantation
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