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indications for bone marrow transplant

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https://www.readbyqxmd.com/read/29348130/setd1a-protects-hscs-from-activation-induced-functional-decline-in-vivo
#1
Kathrin Arndt, Andrea Kranz, Juliane Fohgrub, Adrien Jolly, Anita S Bledau, Michela Di Virgilio, Mathias Lesche, Andreas Dahl, Thomas Höfer, A Francis Stewart, Claudia Waskow
The regenerative capacity of hematopoietic stem cells (HSCs) is limited by the accumulation of DNA damage. Conditional mutagenesis of the histone 3 lysine 4 (H3K4) methyltransferase, Setd1a, revealed that it is required for the expression of DNA damage recognition and repair pathways in HSCs. Specific deletion of Setd1a in adult long-term (LT)-HSCs is compatible with adult life and has little effect on the maintenance of phenotypic LT-HSCs in the bone marrow. However, SETD1A-deficient LT-HSCs lose their transcriptional cellular identity accompanied by loss of their proliferative capacity and stem cell function under replicative stress in situ and after transplantation...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29346436/bone-marrow-concentrate-promotes-bone-regeneration-with-a-suboptimal-dose-of-rhbmp-2
#2
Kazuhiro Egashira, Yoshinori Sumita, Weijian Zhong, Takashi I, Seigo Ohba, Kazuhiro Nagai, Izumi Asahina
Bone marrow concentrate (BMC), which is enriched in mononuclear cells (MNCs) and platelets, has recently attracted the attention of clinicians as a new optional means for bone engineering. We previously reported that the osteoinductive effect of bone morphogenetic protein-2 (BMP-2) could be enhanced synergistically by co-transplantation of peripheral blood (PB)-derived platelet-rich plasma (PRP). This study aims to investigate whether BMC can effectively promote bone formation induced by low-dose BMP-2, thereby reducing the undesirable side-effects of BMP-2, compared to PRP...
2018: PloS One
https://www.readbyqxmd.com/read/29335601/loss-of-cd14-leads-to-disturbed-epithelial-b-cell-crosstalk-and-impairment-of-the-intestinal-barrier-after-e-coli-nissle-monoassociation
#3
Marijana Basic, Manuela Buettner, Lydia M Keubler, Anna Smoczek, Inga Bruesch, Stephanie Buchheister, André Bleich
The TLR4 co-receptor CD14 was identified as an IBD candidate gene. Here, its influence on the intestinal barrier was addressed utilizing E. coli Nissle (EcN), which induces severe inflammation in germfree TLR4-/- mice. After monoassociation, EcN was detected in spleens and livers of TLR4-/- and CD14-/- but not wildtype mice. Barrier impairment was characterized by increased apoptosis and decreased epithelial junction (EJ) expression and was reversed by TLR2 stimulation in CD14-/- mice. Bone marrow (BM) transplantation revealed contribution of hematopoietic and non-hematopoietic cells towards intestinal homeostasis...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29314840/development-of-stem-cell-mobilizing-agents-targeting-cxcr4-receptor-for-peripheral-blood-stem-cell-transplantation-and-beyond
#4
Chien-Huang Wu, Jen-Shin Song, Hsuan-Hao Kuan, Szu-Huei Wu, Ming-Chen Chou, Jiing-Jyh Jan, Lun Kelvin Tsou, Yi-Yu Ke, Chiung-Tong Chen, Kai-Chia Yeh, Sing-Yi Wang, Teng-Kuang Yeh, Chen-Tso Tseng, Chen-Lung Huang, Mine-Hsine Wu, Po-Chu Kuo, Chia-Jui Lee, Kak-Shan Shia
The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4+ cell types from bone marrow to peripheral circulation. We have discovered a novel series of pyrimidine-based CXCR4 antagonists, a representative (i.e., 16) of which was tolerated at a higher dose and showed better HSC-mobilizing ability at the maximal response dose relative to the approved drug 1 (AMD3100), and thus considered a potential drug candidate for PBSCT indication...
January 9, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29312584/recipient-bone-marrow-assimilates-the-myeloid-lymphoid-reconstitution-of-distinct-fetal-hematopoietic-stem-cells
#5
Xiao-Lin Guo, Lei Chu, Fang Ke, Li-Li Mu, Zhen Li, Jie-Jing Cai, Huai-Fang Li, Deng-Li Hong
The fetal liver (FL) is a source of hematopoietic stem and progenitor cells (HSPCs) for transplantation. However, whether FL-HSPCs collected at distinct developmental stages reconstitute similarly or differently in the recipient bone marrow (BM) remains undetermined. We examined this problem in a congeneic mouse transplantation model. We first analyzed the lineage components of FL from 12.5 days post-fertilization (dpf) to 18.5 dpf. The myeloid and lymphoid cells were dynamic in absolute number and ratio. The largest difference was between 12...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311096/early-detection-and-evolution-of-pre-leukemic-clones-in-therapy-related-myeloid-neoplasms-following-autologous-sct
#6
Gerbrig Berger, Leonie I Kroeze, Theresia N Koorenhof-Scheele, Aniek O de Graaf, Kenichi Yoshida, Hiroo Ueno, Yuichi Shiraishi, Satoru Miyano, Eva van den Berg, Hein Schepers, Bert A van der Reijden, Seishi Ogawa, Edo Vellenga, Joop H Jansen
Therapy-related myeloid neoplasms (tMNs) are severe adverse events that can occur following treatment with autologous hematopoietic stem cell transplantation (ASCT). This study aimed to investigate the development of tMN following ASCT at the molecular level by whole exome sequencing (WES) and targeted deep sequencing (TDS) in sequential (pre-) tMN samples. WES identified a significantly higher number of mutations in tMN as compared to de novo MDS (median 27 vs 12, p=0.001). The mutations found in tMN did not carry a clear ageing-signature, unlike the mutations found in de novo MDS, indicating a different mutational mechanism...
January 8, 2018: Blood
https://www.readbyqxmd.com/read/29306107/leukemia-cells-impair-normal-hematopoiesis-and-induce-functionally-loss-of-hematopoietic-stem-cells-through-immune-cells-and-inflammation
#7
Ping Cui, Yuhua Zhang, Maoxiang Cui, Zhihong Li, Guang Ma, Rufeng Wang, Ning Wang, Shujuan Huang, Jie Gao
Bone marrow (BM) failure is often seen in leukemia patients, indicating an abnormal hematopoietic process. However, hematopoiesis in leukemic milieus is largely unknown. In the present study, we utilized one of the most frequent leukemogenic translocations MLL-AF9 to induce leukemia and investigated the hematopoiesis and the activity of hematopoietic stem and progenitor cells (HSPCs) in a leukemic milieu. We found that the phenotypes of the non-leukemic population in leukemic BM were drastically different than normal BM, including blockage of differentiation and a drastically reduced Lin-/Sca+/c-kit+ (LSK) population that contains all HSPCs in leukemic BM...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29296974/urokinase-plasminogen-activator-and-receptor-promote-collagen-induced-arthritis-through-expression-in-hematopoietic-cells
#8
Sherry Thornton, Harini Raghu, Carolina Cruz, Malinda D Frederick, Joseph S Palumbo, Eric S Mullins, Kasper Almholt, Pernille A Usher, Matthew J Flick
The plasminogen activation (PA) system has been implicated in driving inflammatory arthritis, but the precise contribution of PA system components to arthritis pathogenesis remains poorly defined. Here, the role of urokinase plasminogen activator (uPA) and its cognate receptor (uPAR) in the development and severity of inflammatory joint disease was determined using uPA- and uPAR-deficient mice inbred to the strain DBA/1J, a genetic background highly susceptible to collagen-induced arthritis (CIA). Mice deficient in uPA displayed a near-complete amelioration of macroscopic and histological inflammatory joint disease following CIA challenge...
March 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296892/allogeneic-bone-marrow-transplant-in-the-absence-of-cytoreductive-conditioning-rescues-mice-with-%C3%AE-thalassemia-major
#9
Yongliang Huo, Jonathan R Lockhart, Shanrun Liu, Suean Fontenard, Mike Berlett, Thomas M Ryan
β-thalassemia is a group of inherited blood disorders that result in defects in β-globin chain production. Cooley anemia (CA), or β-thalassemia major, is the most severe form of the disease and occurs when an individual has mutations in both copies of the adult β-globin gene. Patients with CA fail to make adult hemoglobin, exhibit ineffective erythropoiesis, experience severe anemia, and are transfusion dependent for life. Currently, allogeneic bone marrow transplantation (BMT) is the only cure; however, few patients have suitable donors for this procedure, which has significant morbidity and mortality...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296815/myeloid-leukemia-factor-1-stabilizes-tumor-suppressor-c-ebp%C3%AE-to-prevent-trib1-driven-acute-myeloid-leukemia
#10
Ikuko Nakamae, Jun-Ya Kato, Takashi Yokoyama, Hidenori Ito, Noriko Yoneda-Kato
C/EBPα is a key transcription factor regulating myeloid differentiation and leukemogenesis. The Trib1-COP1 complex is an E3 ubiquitin ligase that targets C/EBPα for degradation, and its overexpression specifically induces acute myeloid leukemia (AML). Here we show that myeloid leukemia factor 1 (MLF1) stabilizes C/EBPα protein levels by inhibiting the ligase activity of the Trib1-COP1 complex. MLF1 directly interacts with COP1 in the nucleus and interferes with the formation of the Trib1-COP1 complex, thereby blocking its ability to polyubiquitinate C/EBPα for degradation...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296743/hmga2-collaborates-with-jak2v617f-in-the-development-of-myeloproliferative-neoplasms
#11
Koki Ueda, Kazuhiko Ikeda, Takayuki Ikezoe, Kayo Harada-Shirado, Kazuei Ogawa, Yuko Hashimoto, Takahiro Sano, Hiroshi Ohkawara, Satoshi Kimura, Akiko Shichishima-Nakamura, Yuichi Nakamura, Yayoi Shikama, Tsutomu Mori, Philip J Mason, Monica Bessler, Soji Morishita, Norio Komatsu, Kotaro Shide, Kazuya Shimoda, Shuhei Koide, Kazumasa Aoyama, Motohiko Oshima, Atsushi Iwama, Yasuchika Takeishi
High-mobility group AT-hook 2 (HMGA2) is crucial for the self-renewal of fetal hematopoietic stem cells (HSCs) but is downregulated in adult HSCs via repression by MIRlet-7 and the polycomb-recessive complex 2 (PRC2) including EZH2. The HMGA2 messenger RNA (mRNA) level is often elevated in patients with myelofibrosis that exhibits an advanced myeloproliferative neoplasm (MPN) subtype, and deletion of Ezh2 promotes the progression of severe myelofibrosis in JAK2V617F mice with upregulation of several oncogenes such as Hmga2...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29235254/mesenchymal-stem-cells-a-double-edged-sword-in-radiation-induced-lung-injury
#12
Yi Yao, Zhongliang Zheng, Qibin Song
Radiation therapy is an important treatment modality for multiple thoracic malignancies. However, radiation-induced lung injury (RILI), which is the term generally used to describe damage to the lungs caused by exposure to ionizing radiation, remains a critical issue affecting both tumor control and patient quality of life. Despite tremendous effort, there is no current consensus regarding the optimal treatment approach for RILI. Because of a number of functional advantages, including self-proliferation, multi-differentiation, injury foci chemotaxis, anti-inflammation, and immunomodulation, mesenchymal stem cells (MSCs) have been a focus of research for many years...
December 13, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29228600/non-invasive-in-vivo-molecular-imaging-of-intra-articularly-transplanted-immortalized-bone-marrow-stem-cells-for-osteoarthritis-treatment
#13
Bou-Yue Peng, Chi-Sheng Chiou, Navneet Kumar Dubey, Sung-Hsun Yu, Yue-Hua Deng, Feng-Chou Tsai, Han-Sun Chiang, Ying-Hua Shieh, Wei-Hong Chen, Win-Ping Deng
Pathophysiology of osteoarthritis (OA) is characterized by progressive loss of articular cartilage in the knee-joints. To impart regenerative ability in lowly metabolizing chondrocytes, the bone marrow stem cells (BMSCs) has recently been recognized as a superior alternative treatment for OA. However, study of primary BMSCs-mediated chondrogenesis is difficult due to progressive cellular aging and replicative senescence. To obtain a therapeutic cell population for OA, BMSCs were immortalized by human papilloma virus (HPV)-16 E6/E7 along with mCherry luciferase (mCL), a gene marker for non-invasive imaging, and designated as iBMSCs-mCL...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29226242/intracerebroventricular-delivery-of-hematopoietic-progenitors-results-in-rapid-and-robust-engraftment-of-microglia-like-cells
#14
Alessia Capotondo, Rita Milazzo, Jose M Garcia-Manteiga, Eleonora Cavalca, Annita Montepeloso, Brian S Garrison, Marco Peviani, Derrick J Rossi, Alessandra Biffi
Recent evidence indicates that hematopoietic stem and progenitor cells (HSPCs) can serve as vehicles for therapeutic molecular delivery to the brain by contributing to the turnover of resident myeloid cell populations. However, such engraftment needs to be fast and efficient to exert its therapeutic potential for diseases affecting the central nervous system. Moreover, the nature of the cells reconstituted after transplantation and whether they could comprise bona fide microglia remain to be assessed. We demonstrate that transplantation of HSPCs in the cerebral lateral ventricles provides rapid engraftment of morphologically, antigenically, and transcriptionally dependable microglia-like cells...
December 2017: Science Advances
https://www.readbyqxmd.com/read/29222849/bone-marrow-transplantation-improves-motor-activity-in-a-mouse-model-of-ataxia
#15
David Díaz, Marina Piquer-Gil, Javier Sánchez Recio, María Magdalena Martínez-Losa, José Ramón Alonso, Eduardo Weruaga, Manuel Álvarez-Dolado
Ataxias are locomotor disorders that can have an origin both neural and muscular, although both impairments are related. Unfortunately, ataxia has no cure and the current therapies are aimed at motor re-education or muscular reinforcement. Nevertheless, cell therapy is becoming a promising approach to deal with incurable neural diseases, including neuro-muscular ataxias. Here we have used a model of ataxia, the PCD mutant mouse, to study the effect of healthy (wild-type) bone marrow transplantation on the restoration of defective mobility...
December 8, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29217821/il-11-promotes-the-treatment-efficacy-of-hematopoietic-stem-cell-transplant-therapy-in-aplastic-anemia-model-mice-through-a-nf-%C3%AE%C2%BAb-microrna-204-thrombopoietin-regulatory-axis
#16
Yan Wang, Zhi-Yun Niu, Yu-Jie Guo, Li-Hua Wang, Feng-Ru Lin, Jing-Yu Zhang
Hematopoietic stem cell (HSC) transplantation could be of therapeutic value for aplastic anemia (AA) patients, and immunosuppressants may facilitate the efficiency of the procedure. As anti-inflammatory cytokine interleukin-11 (IL-11) has a thrombopoietic effect, its use in cases of chronic bone marrow failure, such as AA, has been proposed to induce HSC function. However, the putative mechanisms that may support this process remain poorly defined. We found that decreased miR-204-5p levels were coincident with increased proliferation in mouse HSCs following exposure to IL-11 in vitro...
December 8, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29212909/pd-l1-prevents-the-development-of-autoimmune-heart-disease-in-graft-versus-host-disease
#17
Kathryn W Juchem, Faruk Sacirbegovic, Cuiling Zhang, Arlene H Sharpe, Kerry Russell, Jennifer M McNiff, Anthony J Demetris, Mark J Shlomchik, Warren D Shlomchik
Effector memory T cells (TEM) are less capable of inducing graft-versus-host disease (GVHD) compared with naive T cells (TN). Previously, in the TS1 TCR transgenic model of GVHD, wherein TS1 CD4 cells specific for a model minor histocompatibility Ag (miHA) induce GVHD in miHA-positive recipients, we found that cell-intrinsic properties of TS1 TEM reduced their GVHD potency relative to TS1 TN Posttransplant, TS1 TEM progeny expressed higher levels of PD-1 than did TS1 TN progeny, leading us to test the hypothesis that TEM induce less GVHD because of increased sensitivity to PD-ligands...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29207878/cd20-cd19-bispecific-car-t-cells-for-the-treatment-of-b-cell-malignancies
#18
Alexandra Martyniszyn, Ann-Christin Krahl, Maya C André, Andreas A Hombach, Hinrich Abken
The treatment of leukemia/lymphoma by chimeric antigen receptor (CAR) redirected T cells with specificity for CD19 induced complete remissions in the majority of patients with a realistic hope for cure. However, recent follow-up data revealed a substantial risk of relapse through leukemic cells which lack the CAR targeted antigen. In this situation a bispecific CAR with binding domains for CD19 and CD20 is aimed at recognizing also leukemic cells with only one cognate antigen. The anti-CD20-CD19 bispecific CAR induced a full T cell response upon engagement of CD19 or CD20 on target cells showing a true "OR" gate recognition in redirecting T cell activation...
December 5, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29207730/safety-assessment-of-human-bone-marrow-derived-mesenchymal-stromal-cells-transplantation-in-wistar-rats
#19
Ashwini P Aithal, Laxminarayana Kurady Bairy, Raviraja N Seetharam
Introduction: Bone Marrow-derived Mesenchymal Stromal Cells (BM-MSCs) are multipotent stem cells isolated from adult human bone marrow. Properties of MSCs make them potentially ideal candidates for regenerative medicine. The preclinical data available in the literature regarding the safety assessment of MSCs at different dosage group is scanty. Aim: To evaluate the safety of BM-MSCs transplantation in Wistar rats. Materials and Methods: Eighteen adult female Wistar rats were used in the study...
September 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/29207024/geraniin-protects-bone-marrow%C3%A2-derived-mesenchymal-stem-cells-against-hydrogen-peroxide%C3%A2-induced-cellular-oxidative-stress-in-vitro
#20
Dan Huang, Li Yin, Xinxin Liu, Bo Lv, Zulong Xie, Xuedong Wang, Bo Yu, Yao Zhang
Administration of bone marrow‑derived mesenchymal stem cells (MSCs) has emerged as a potential therapeutic approach for the treatment of myocardial infarction (MI). However, the increase in reactive oxygen species (ROS) in ischemic cardiac tissue compromises the survival of transplanted MSCs, thus resulting in limited therapeutic efficiency. Therefore, strategies that attenuate oxidative stress‑induced damage and enhance MSC viability are required. Geraniin has been reported to possess potent antioxidative activity and exert protective effects on numerous cell types under certain conditions...
February 2018: International Journal of Molecular Medicine
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