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Bone marrow engraftment

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https://www.readbyqxmd.com/read/29027623/prospective-observational-study-on-the-first-51-cases-of-peripheral-blood-stem-cell-transplantation-from-unrelated-donors-in-japan
#1
Tatsunori Goto, Takashi Tanaka, Masashi Sawa, Yasunori Ueda, Hiroatsu Ago, Shigeru Chiba, Heiwa Kanamori, Akinori Nishikawa, Masaharu Nougawa, Kazuteru Ohashi, Hirokazu Okumura, Mitsune Tanimoto, Takahiro Fukuda, Naomi Kawashima, Tomonori Kato, Kazuya Okada, Koji Nagafuji, Shin-Ichiro Okamoto, Yoshiko Atsuta, Masayuki Hino, Junji Tanaka, Koichi Miyamura
The Japan Marrow Donor Program (JMDP) has facilitated unrelated peripheral blood stem cell transplantation (URPBSCT) since 2010. We conducted a prospective multicenter observational study to evaluate the feasibility of such transplantation. Between 2011 and 2014, 51 patients underwent URPBSCT from 8/8 allele-matched donors for hematological malignancies. The median age of the patients was 50 years; 21 had high-risk disease. Myeloablative conditioning regimens were used in 31 patients, and tacrolimus based graft-versus-host disease (GVHD) prophylaxis was used for all patients...
October 13, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29016733/endothelial-to-haematopoietic-transition-contributes-to-pulmonary-arterial-hypertension
#2
Olin D Liang, Eui-Young So, Pamela C Egan, Laura R Goldberg, Jason M Aliotta, Keith Q Wu, Patrycja M Dubielecka, Corey E Ventetuolo, Anthony M Reginato, Peter J Quesenberry, James R Klinger
Aims: The pathogenic mechanisms of pulmonary arterial hypertension (PAH) remain unclear, but involve dysfunctional endothelial cells (ECs), dysregulated immunity and inflammation in the lung. We hypothesize that a developmental process called endothelial to haematopoietic transition (EHT) contributes to the pathogenesis of pulmonary hypertension (PH). We sought to determine the role of EHT in mouse models of PH, to characterize specific cell types involved in this process, and to identify potential therapeutic targets to prevent disease progression...
September 7, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28991922/clonal-dominance-and-transplantation-dynamics-in-hematopoietic-stem-cell-compartments
#3
Peter Ashcroft, Markus G Manz, Sebastian Bonhoeffer
Hematopoietic stem cells in mammals are known to reside mostly in the bone marrow, but also transitively passage in small numbers in the blood. Experimental findings have suggested that they exist in a dynamic equilibrium, continuously migrating between these two compartments. Here we construct an individual-based mathematical model of this process, which is parametrised using existing empirical findings from mice. This approach allows us to quantify the amount of migration between the bone marrow niches and the peripheral blood...
October 9, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28985760/an-improved-pre-clinical-patient-derived-liquid-xenograft-mouse-model-for-acute-myeloid-leukemia
#4
Zhisheng Her, Kylie Su Mei Yong, Kathirvel Paramasivam, Wilson Wei Sheng Tan, Xue Ying Chan, Sue Yee Tan, Min Liu, Yong Fan, Yeh Ching Linn, Kam Man Hui, Uttam Surana, Qingfeng Chen
BACKGROUND: Xenotransplantation of patient-derived AML (acute myeloid leukemia) cells in NOD-scid Il2rγ (null) (NSG) mice is the method of choice for evaluating this human hematologic malignancy. However, existing models constructed using intravenous injection in adult or newborn NSG mice have inferior engraftment efficiency, poor peripheral blood engraftment, or are difficult to construct. METHODS: Here, we describe an improved AML xenograft model where primary human AML cells were injected into NSG newborn pups intrahepatically...
October 6, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28985203/cell-therapy-for-diverse-central-nervous-system-disorders-inherited-metabolic-diseases-and-autism
#5
REVIEW
Jessica M Sun, Joanne Kurtzberg
The concept of utilizing human cells for the treatment of medical conditions is not new. In its simplest form, blood product transfusion as treatment of severe hemorrhage has been practiced since the 1800s. The advent of hematopoietic stem cell transplantation (HSCT) began with the development of bone marrow transplantation for hematologic malignancies in the mid-1900s and is now standard of care for many hematologic disorders. In the past few decades, HSCT has expanded to additional sources of donor cells, a wider range of indications, and the development of novel cell products...
October 6, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28974505/hematopoietic-stem-cell-transplantation-rescues-the-hematological-immunological-and-vascular-phenotype-in-dada2
#6
Hasan Hashem, Ashish R Kumar, Ingo Müller, Florian Babor, Robbert Bredius, Jignesh Dalal, Amy P Hsu, Steven M Holland, Dennis D Hickstein, Stephen Jolles, Robert Krance, Ghadir Sasa, Mervi Taskinen, Minna Koskenvuo, Janna Saarela, Joris van Montfrans, Keith Wilson, Barbara Bosch, Leen Moens, Michael Hershfield, Isabelle Meyts
Deficiency of adenosine deaminase 2 (DADA2) is caused by biallelic deleterious mutations in CECR1 DADA2 results in variable autoinflammation and vasculopathy (recurrent fevers, livedo reticularis, polyarteritis nodosa, lacunar ischemic strokes and intracranial hemorrhages), immunodeficiency and bone marrow failure. TNF-α blockade is the treatment of choice for the autoinflammation and vascular manifestations. Hematopoietic stem cell transplantation (HSCT) represents a potential definitive treatment. We present a cohort of 14 patients from 6 countries who received HSCT for DADA2...
October 3, 2017: Blood
https://www.readbyqxmd.com/read/28956132/vegf-angpt1-angpt2-and-mmp-9-expression-in-the-autologous-hematopoietic-stem-cell-transplantation-and-its-impact-on-the-time-to-engraftment
#7
Mateusz Nowicki, Agnieszka Wierzbowska, Roman Małachowski, Tadeusz Robak, Olga Grzybowska-Izydorczyk, Agnieszka Pluta, Anna Szmigielska-Kapłon
As a site of complicated interactions among cytokines, bone marrow niche has been the subject of many scientific studies, mainly in the context of the proteins influencing damage or recovery of endothelium after allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we aimed at exploring mutual correlations of bone marrow niche cytokines involved in the homing and mobilization of hematopoietic stem cells, as well as in angiogenesis. The aim of our study was to evaluate levels of cytokines: VEGF, angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), and matrix metalloproteinase 9 (MMP-9) during autologous HSCT and to examine their influence on hematological recovery...
September 27, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28944999/systemic-redistribution-of-the-intramyocardially-injected-mesenchymal-stem-cells-by-repeated-remote-ischaemic-post-conditioning
#8
Qin Jiang, Tao Yu, Keli Huang, Hao Zhang, Zhe Zheng, Shengshou Hu
We investigated the effect of repeated remote ischaemic post-conditioning (RIPoC) on the organ distribution of the intramyocardially injected MSCs in rat myocardial ischemia model. Myocardial ischemia of adult female Sprague-Dawley rats was induced by 30-min. obstruction of the left anterior descending coronary artery. Repeated RIPoC was induced after ischemia with three cycles of 5-min. occlusion and reperfusion of the limb with the frequency of half a day, 1 or 2 days, respectively. Compared with that by single RIPoC, repeated RIPoC transiently reduced oxidative stress, lipid peroxidation and inflammation in ischaemic myocardium; the gene expression of stromal cell-derived factor-1 alpha (SDF-1α) was consistently induced by repeated RIPoC procedures...
September 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28933777/generation-and-use-of-a-humanized-bone-marrow-ossicle-niche-for-hematopoietic-xenotransplantation-into-mice
#9
Andreas Reinisch, David Cruz Hernandez, Katharina Schallmoser, Ravindra Majeti
Xenotransplantation is frequently used to study normal and malignant hematopoiesis of human cells. However, conventional mouse xenotransplantation models lack essential human-specific bone-marrow (BM)-microenvironment-derived survival, proliferation, and self-renewal signals for engraftment of normal and malignant blood cells. As a consequence, many human leukemias and other hematologic disorders do not robustly engraft in these conventional models. Here, we describe a complete workflow for the generation of humanized ossicles with an accessible BM microenvironment that faithfully recapitulates normal BM niche morphology and function...
October 2017: Nature Protocols
https://www.readbyqxmd.com/read/28899758/chronic-global-analysis-of-vascular-permeability-and-cerebral-blood-flow-after-bone-marrow-stromal-cell-treatment-of-traumatic-brain-injury-in-the-rat-a-long-term-mri-study
#10
Lian Li, Michael Chopp, Guangliang Ding, Qingjiang Li, Asim Mahmood, Quan Jiang
Vascular permeability and hemodynamic alteration in response to the transplantation of human bone marrow stromal cells (hMSCs) after traumatic brain injury (TBI) were longitudinally investigated in non directly injured and normal-appearing cerebral tissue using magnetic resonance imaging (MRI). Male Wistar rats (300-350g, n=30) subjected to controlled cortical impact TBI were intravenously injected with 1ml of saline (at 6-h or 1-week post-injury, n=5/group) or with hMSCs in suspension (∼3×10(6) hMSCs, at 6-h or 1-week post-injury, n=10/group)...
November 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28895851/gene-therapy-approaches-to-hemoglobinopathies
#11
REVIEW
Giuliana Ferrari, Marina Cavazzana, Fulvio Mavilio
Gene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with a lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Preclinical and early clinical studies showed the safety and potential efficacy of this therapeutic approach as well as the hurdles still limiting its general application. In addition, for both beta-thalassemia and sickle cell disease, an altered bone marrow microenvironment reduces the efficiency of stem cell harvesting as well as engraftment...
October 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28895846/in%C3%A2-vivo-hematopoietic-stem-cell-transduction
#12
REVIEW
Maximilian Richter, Daniel Stone, Carol Miao, Olivier Humbert, Hans-Peter Kiem, Thalia Papayannopoulou, André Lieber
Current protocols for hematopoietic stem cell (HSC) gene therapy, involving the transplantation of ex vivo lentivirus vector-transduced HSCs into myeloablated recipients, are complex and not without risk for the patient. In vivo HSC gene therapy can be achieved by the direct modification of HSCs in the bone marrow after intraosseous injection of gene delivery vectors. A recently developed approach involves the mobilization of HSCs from the bone marrow into peripheral the blood circulation, intravenous vector injection, and re-engraftment of genetically modified HSCs in the bone marrow...
October 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28892146/murine-retrovirally-transduced-bone-marrow-engraftment-models-of-mll-fusion-driven-acute-myelogenous-leukemias-aml
#13
Matthew C Stubbs, Andrei V Krivtsov
MLL-rearranged leukemia represents approximately 5% to 10% of adult acute myelogenous leukemia (AML) and nearly half of all infant/pediatric acute leukemia cases. These leukemias have a poor prognosis, and there are no approved therapeutic options. The rearrangement in the MLL gene leads to aberrant expression of MLL-fusion proteins. These are transforming in murine bone marrow and, in particular, on stem cells and myeloid progenitors derived from bone marrow or fetal liver. The commonality of the MLL fusions is the in-frame fusion of 8 to 11 N-terminal exons of MLL1 (KMT2a) with the C-terminus of a partner fusion gene...
September 11, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/28892085/circulating-endothelial-cell-count-a-reliable-marker-of-endothelial-damage-in-patients-undergoing-hematopoietic-stem-cell-transplantation
#14
C Almici, C Skert, B Bruno, A Bianchetti, R Verardi, A Di Palma, A Neva, S Braga, G Piccinelli, G Piovani, M Malagola, S Bernardi, L Giaccone, L Brunello, M Festuccia, K Baeten, D Russo, M Marini
The physio-pathologic interrelationships between endothelium and GvHD have been better elucidated and have led to definition of the entity 'endothelial GvHD' as an essential early phase prior to the clinical presentation of acute GvHD. Using the CellSearch system, we analyzed circulating endothelial cells (CEC) in 90 allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients at the following time-points: T1 (pre-conditioning), T2 (pre-transplant), T3 (engraftment), T4 (onset of GvHD) and T5 (1 week after steroid treatment)...
September 11, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28878134/prevention-of-breast-cancer-skeletal-metastases-with-parathyroid-hormone
#15
Srilatha Swami, Joshua Johnson, Lance A Bettinson, Takaharu Kimura, Hui Zhu, Megan A Albertelli, Rachelle W Johnson, Joy Y Wu
Advanced breast cancer is frequently associated with skeletal metastases and accelerated bone loss. Recombinant parathyroid hormone [teriparatide, PTH(1-34)] is the first anabolic agent approved in the US for treatment of osteoporosis. While signaling through the PTH receptor in the osteoblast lineage regulates bone marrow hematopoietic niches, the effects of anabolic PTH on the skeletal metastatic niche are unknown. Here, we demonstrate, using orthotopic and intratibial models of 4T1 murine and MDA-MB-231 human breast cancer tumors, that anabolic PTH decreases both tumor engraftment and the incidence of spontaneous skeletal metastasis in mice...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28869617/a-phase-1-trial-of-90-y-zevalin-radioimmunotherapy-with-autologous-stem-cell-transplant-for-multiple-myeloma
#16
A Dispenzieri, A D'Souza, M A Gertz, K Laumann, G Wiseman, M Q Lacy, B LaPlant, F Buadi, S R Hayman, S K Kumar, D Dingli, W J Hogan, S M Ansell, D A Gastineau, D J Inwards, I N Micallef, L F Porrata, P B Johnston, M R Litzow, T E Witzig
This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan ((90)Y-Zevalin) with high dose melphalan (HDM) therapy in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). In a 3+3 trial design, 30 patients received rituximab 250 mg/m(2) with indium-111 ibritumomab tiuxetan ((111)In-Zevalin) for dosimetry (day -22); rituximab 250 mg/m(2) with escalating doses of (90)Y-Zevalin (day -14); melphalan 100 mg/m(2) (days -2,-1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment...
October 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28861453/data-on-the-effect-of-oral-feeding-of-arachidonic-acid-or-docosahexanoic-acid-on-haematopoiesis-in-mice
#17
Kedar Limbkar, Ankita Dhenge, Dipesh D Jadhav, Hirekodathakallu V Thulasiram, Vaijayanti Kale, Lalita Limaye
Stem cells have peculiar property to self-renew and differentiate. It is important to control their fate in safe and effective ways for their therapeutic use. The mediators of essential polyunsaturated fatty acids (PUFAs) namely Arachidonic acid (AA) and Docosahexanoic acid (DHA) are known to play a role in haematopoiesis via various metabolic pathways [1]. However the direct effect of purified AA or DHA on haematopoiesis has not been well investigated yet. We have reported that oral administration of PUFAs enhanced haematopoiesis in mice [2]...
October 2017: Data in Brief
https://www.readbyqxmd.com/read/28860501/in-vivo-immune-interactions-of-multipotent-stromal-cells-underlie-their-long-lasting-pain-relieving-effect
#18
Wei Guo, Satoshi Imai, Jia-Le Yang, Shiping Zou, Mineo Watanabe, Yu-Xia Chu, Zaid Mohammad, Huakun Xu, Kamal D Moudgil, Feng Wei, Ronald Dubner, Ke Ren
Systemic infusion of bone marrow stromal cells (BMSCs), a major type of multipotent stromal cells, produces pain relief (antihyperalgesia) that lasts for months. However, studies have shown that the majority of BMSCs are trapped in the lungs immediately after intravenous infusion and their survival time in the host is inconsistent with their lengthy antihyperalgesia. Here we show that long-lasting antihyperalgesia produced by BMSCs required their chemotactic factors such as CCL4 and CCR2, the integrations with the monocytes/macrophages population, and BMSC-induced monocyte CXCL1...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28860000/pre-engraftment-bloodstream-infections-after-allogeneic-hematopoietic-cell-transplantation-impact-of-t-cell-replete-transplantation-from-a-haploidentical-donor
#19
Malgorzata Mikulska, Anna Maria Raiola, Federica Galaverna, Elisa Balletto, Maria Lucia Borghesi, Riccardo Varaldo, Francesca Gualandi, Livia Giannoni, Giordana Pastori, Daniele Roberto Giacobbe, Alessio Signori, Valerio Del Bono, Claudio Viscoli, Andrea Bacigalupo, Emanuele Angelucci
Bloodstream infections (BSIs) are frequent and important infectious complications after hematopoietic cell transplantation (HCT). The aim of this study was to analyze the incidence, risk factors, and outcome of pre-engraftment BSIs after allogeneic HCT. We retrospectively analyzed data from 553 consecutive patients who underwent HCT between 2010 and 2016 was performed. Sixty percent of the patients received T cell-replete unmanipulated haploidentical bone marrow with high-dose post-transplantation cyclophosphamide...
August 30, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28842629/bone-marrow-derived-cells-and-their-conditioned-medium-induce-microvascular-repair-in-uremic-rats-by-stimulation-of-endogenous-repair-mechanisms
#20
Lina Golle, Hans U Gerth, Katrin Beul, Barbara Heitplatz, Peter Barth, Manfred Fobker, Hermann Pavenstädt, Giovana S Di Marco, Marcus Brand
The reduced number of circulating stem/progenitor cells that is found in chronic kidney disease (CKD) patients may contribute to impaired angiogenic repair and decreased capillary density in the heart. Cell therapy with bone marrow-derived cells (BMDCs) has been shown to induce positive effects on the microvasculature and cardiac function, most likely due to secretion of growth factors and cytokines, all of which are present in the conditioned medium (CM); however, this is controversial. Here we showed that treatment with BMDC or CM restored vascular density and decreased the extent of fibrosis in a rat model of CKD, the 5/6 nephrectomy...
August 25, 2017: Scientific Reports
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