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Hematopoietic stem cells

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https://www.readbyqxmd.com/read/29353324/stromalized-microreactor-supports-murine-hematopoietic-progenitor-enrichment
#1
Danika Khong, Matthew Li, Amy Singleton, Ling-Yee Chin, Biju Parekkadan
There is an emerging need to process, expand, and even genetically engineer hematopoietic stem and progenitor cells (HSPCs) prior to administration for blood reconstitution therapy. A closed-system and automated solution for ex vivo HSC processing can improve adoption and standardize processing techniques. Here, we report a recirculating flow bioreactor where HSCs are stabilized and enriched for short-term processing by indirect fibroblast feeder coculture. Mouse 3 T3 fibroblasts were seeded on the extraluminal membrane surface of a hollow fiber micro-bioreactor and were found to support HSPC cell number compared to unsupported BMCs...
January 20, 2018: Biomedical Microdevices
https://www.readbyqxmd.com/read/29353275/endocrine-and-metabolic-disturbances-in-survivors-of-hematopoietic-stem-cell-transplantation-in-childhood-and-adolescence
#2
Shlomit Shalitin, Lihi Pertman, Michal Yackobovitch-Gavan, Isaac Yaniv, Yael Lebenthal, Moshe Phillip, Jerry Stein
BACKGROUND/AIMS: The objective was to evaluate endocrine complications in survivors of hematopoietic stem cell transplantation (HSCT) performed during childhood. METHODS: Endocrine dysfunction and metabolic syndrome parameters were assessed by chart review of 178 childhood HSCT survivors (median age at evaluation, 15.5 [range: 3.8-29.8] years; median follow-up, 8.5 [range: 2-23.4] years). RESULTS: The following statistically significant associations were identified (p < 0...
January 19, 2018: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/29353110/orchestration-of-chemomobilization-and-g-csf-administration-for-successful-hematopoietic-stem-cell-collection
#3
Katharina Kriegsmann, Anita Schmitt, Mark Kriegsmann, Thomas Bruckner, Adamma Anyanwu, Mathias Witzens-Harig, Carsten Müller-Tidow, Stefan Klein, Patrick Wuchter
Successful collection of peripheral blood stem cells (PBSCs) depends on the optimal orchestration of mobilization chemotherapy, granulocyte-colony-stimulating factor (G-CSF) application, and CD34+ cell number assessment in the peripheral blood (PB). However, determining the optimal timing in accordance to the applied chemomobilization regimen can be challenging. While most centers apply their own local timing schedules, a reliable timetable including the currently most often used mobilization regimens is lacking...
January 15, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29353058/chd7-is-critical-for-early-t-cell-development-and-thymus-organogenesis-in-zebrafish
#4
Zhi-Zhi Liu, Zi-Long Wang, Tae-Ik Choi, Wen-Ting Huang, Han-Tsing Wang, Ying-Ying Han, Lou-Yin Zhu, Hyun-Taek Kim, Jung-Hwa Choi, Jin-Soo Lee, Hyung-Goo Kim, Jian Zhao, Yue Chen, Zhuo Lu, Xiao-Li Tian, Bing-Xing Pan, Bao-Ming Li, Cheol-Hee Kim, Hong Xu
CHARGE syndrome is a congenital disorder affecting multiple organs and mainly caused by mutations in CHD7, a gene encoding a chromatin-remodeling protein. Immunodeficiency and reduced T-cells have been noted in CHARGE syndrome. However, the mechanisms underlying T-lymphopenia are largely unexplored. Here, we observed dramatic decrease of T cells in both chd7-knockdown and -knockout zebrafish embryos. Unexpectedly, hematopoietic stem and progenitor cells and, particularly, lymphoid progenitor cells were increased peripherally in nonthymic areas in chd7-deficient embryos, unlikely to contribute to the T cell decrease...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29352666/handling-processing-and-disposal-of-stem-cell-products-in-europe-a-survey-by-the-cellular-therapy-and-immunobiology-working-party-of-the-european-society-for-blood-and-marrow-transplantation
#5
Andreas Holbro, Helen Baldomero, Francesco Lanza, Christian Chabannon, John A Snowden, Andreas Buser, Laura Infanti, Nina Worel, Anna Sureda, Manuela Badoglio, Jakob Passweg, Chiara Bonini
BACKGROUND: There is considerable heterogeneity in processing of stem cells for hematopoietic stem cell transplantation across Europe. The Foundation for the Accreditation of Cellular Therapy (FACT)-Joint Accreditation Committee International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation (EBMT) (JACIE) standards provide minimum guidelines that, however, leave room for significant variations in practices at the individual transplantation center (TC)...
January 15, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29351987/cd83-is-a-new-potential-biomarker-and-therapeutic-target-for-hodgkin-lymphoma
#6
Ziduo Li, Xinsheng Ju, Kenneth Lee, Candice Clarke, Jennifer L Hsu, Edward Abadir, Christian E Bryant, Suzanne Pears, Neroli Sunderland, Scott Heffernan, Annemarie Hennessy, Tsun-Ho Lo, Geoffrey A Pietersz, Fiona Kupresanin, Phillip D Fromm, Pablo A Silveira, Con Tsonis, Wendy A Cooper, Ilona Cunningham, Christina Brown, Georgina J Clark, Derek N J Hart
Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. We demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and interestingly, the trogocytosing CD83+T cells expressed significantly more PD-1 compared to CD83- T cells...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351985/tocilizumab-tacrolimus-and-methotrexate-for-the-prevention-of-acute-graft-versus-host-disease-low-incidence-of-lower-gastrointestinal-tract-disease
#7
William R Drobyski, Aniko Szabo, Fenlu Zhu, Carolyn Keever-Taylor, Kyle M Hebert, Renee Dunn, Sharon Yim, Bryon Johnson, Anita D'Souza, Mary Eapen, Timothy S Fenske, Parameswaran Hari, Mehdi Hamadani, Mary M Horowitz, J Douglas Rizzo, Wael Saber, Nirav Shah, Bronwen Shaw, Marcelo Pasquini
We conducted a phase 2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation received Tocilizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft versus host disease prophylaxis. Thirty-five patients were enrolled between January 2015 and June 2016. The median age of the cohort was 66 (range 22-76). All patients received busulfan-based conditioning, and were transplanted with HLA-matched related or matched unrelated bone marrow or peripheral stem cell grafts...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351753/mesenchymal-stem-cells-show-functional-defect-and-decreased-anti-cancer-effect-after-exposure-to-chemotherapeutic-drugs
#8
Chinnapaka Somaiah, Atul Kumar, Renu Sharma, Amit Sharma, Trishna Anand, Jina Bhattacharyya, Damodar Das, Sewali Deka Talukdar, Bithiah Grace Jaganathan
BACKGROUND: Mesenchymal stem cells (MSC) are used for several therapeutic applications to improve the functions of bone, cardiac, nervous tissue as well as to facilitate the repopulation of hematopoietic stem cells. MSC give rise to the non-hematopoietic stromal cells of the bone marrow and are important for the maintenance of normal hematopoiesis. Chemotherapeutic drugs used for treatment of leukemia extensively damage the stromal cells and alter their gene expression profiles. METHODS: We determined the changes in adipogenic, osteogenic differentiation, phenotypic and gene expression in MSC during treatment with chemotherapeutic drugs cytarabine, daunorubicin and vincristine...
January 19, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29350710/exercise-intervention-attrition-compliance-adherence-and-progression-following-hematopoietic-stem-cell-transplantation%C3%A2
#9
Tara Peters, Ruby Erdmann, Eileen Danaher Hacker
BACKGROUND: Exercise is widely touted as an effective intervention to optimize health and well-being after high-dose chemotherapy and hematopoietic stem cell transplantation. 
. OBJECTIVES: This article reports attrition, compliance, adherence, and progression from the strength training arm of the single-blind randomized, controlled trial Strength Training to Enhance Early Recovery (STEER). 
. METHODS: 37 patients were randomized to the intervention and participated in a structured strength training program introduced during hospitalization and continued for six weeks after release...
February 1, 2018: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/29350698/identification-and-management-sinusoidal-obstruction-syndrome-veno-occlusive-disease-eelated-to-hematopoietic-stem-cell-transplantation%C3%A2
#10
Mairéad Ní Chonghaile, Karen Wolownik
BACKGROUND: Sinusoidal obstruction syndrome (SOS), also called hepatic veno-occlusive disease (VOD), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) that affects about 1 in 7 patients undergoing this procedure. SOS/VOD is caused by the conditioning regimens administered prior to HSCT; in some cases, SOS/VOD results from chemotherapy alone. SOS/VOD usually develops within three weeks following HSCT; however, it can have later onset. 
...
February 1, 2018: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/29350534/discovery-of-tetrahydroisoquinoline-containing-cxcr4-antagonists-with-improved-in-vitro-admet-properties
#11
Eric J Miller, Edgars Jecs, Valarie M Truax, Brooke M Katzman, Yesim A Tahirovic, Robert J Wilson, Katie M Kuo, Michelle B Kim, Huy H Nguyen, Manohar T Saindane, Huanyu Zhao, Tao Wang, Chi S Sum, Mary Ellen Cvijic, Gretchen M Schroeder, Lawrence J Wilson, Dennis C Liotta
CXCR4 is a 7-transmembrane receptor expressed by hematopoietic stem cells and progeny, as well as by ≥ 48 different cancers types. CXCL12, the only chemokine ligand of CXCR4, is secreted within the tumor microenvironment, providing sanctuary for CXCR4+ tumor cells from immune surveillance and chemotherapeutic elimination by 1) stimulating pro-survival signaling and 2) recruiting CXCR4+ immunosuppressive leukocytes. Additionally, distant CXCL12-rich niches attract and support CXCR4+ metastatic growths. Accordingly, CXCR4 antagonists can potentially obstruct CXCR4-mediated pro-survival signaling, recondition the CXCR4+ leukocyte infiltrate from immunosuppressive to immunoreactive, and inhibit CXCR4+ cancer cell metastasis...
January 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29350494/sleep-disruption-in-caregivers-of-pediatric-stem-cell-recipients
#12
Kristen Coleman, Laura Flesch, Lisa Petiniot, Abigail Pate, Li Lin, Lori Crosby, Dean W Beebe, Adam Nelson, Priscila Badia Alonso, Stella M Davies, Rachel B Baker, Christopher E Dandoy
Parents/caregivers of hospitalized patients are at risk of sleep disruption. We performed a cross-sectional quantitative and qualitative evaluation of sleep in parents/caregivers of children undergoing hematopoietic stem cell transplant (HSCT; n = 17). Additionally, we explored the frequency of room entries for hospitalized patients undergoing HSCT (n = 189 nights). Twelve caregivers (71%) demonstrated significant sleep disturbance, 12 (71%) described sleep quality as poor, 15 (88%) averaged < 6 hours of sleep per night, 14 (82%) awakened at least four times per night...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29350425/the-impact-of-preapheresis-white-blood-cell-count-on-autologous-peripheral-blood-stem-cell-collection-efficiency-and-hsc-infusion-side-effect-rate
#13
Araci M Sakashita, Andrea T Kondo, Ana Paula H Yokoyama, Sanny M C Lira, Carolina B Bub, Aline M Souza, Andrea N F Cipolletta, Kelen C Alvarez, Nelson Hamerschlak, Jose M Kutner, Carlos S Chiattone
BACKGROUND: Autologous peripheral blood hematopoietic stem cell (PBSC) collection efficiency (CE) is reportedly affected by the patient's blood properties; however, studies to identify factors correlated with CE have shown inconsistent results. Additionally, variables such as stem cell graft granulocyte content and patient age, sex, and underlying disease, may be associated with hematopietic stem cell (HSC) infusion-related adverse reactions. In this study, we evaluated the correlation of preleukapheresis PB granulocyte count and PBSC harvest variables with CD34+ collection yield and efficiency, and thawed HSC infusion side effect occurrence...
January 19, 2018: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/29349923/magnetic-macroporous-hydrogels-as-a-novel-approach-for-perfused-stem-cell-culture-in-3d-scaffolds-via-contactless-motion-control
#14
Lisa Rödling, Esther Magano Volz, Annamarija Raic, Katharina Brändle, Matthias Franzreb, Cornelia Lee-Thedieck
There is an urgent need for 3D cell culture systems that avoid the oversimplifications and artifacts of conventional culture in 2D. However, 3D culture within the cavities of porous biomaterials or large 3D structures harboring high cell numbers is limited by the needs to nurture cells and to remove growth-limiting metabolites. To overcome the diffusion-limited transport of such soluble factors in 3D culture, mixing can be improved by pumping, stirring or shaking, but this in turn can lead to other problems...
January 19, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29349879/a-novel-pklr-gene-mutation-identified-using-advanced-molecular-techniques
#15
Yunyan He, Jianming Luo, Yonghong Lei, Siyuan Jia, Ning Liao
This study's purposes were to diagnose intractable hemolytic anemia and to provide guiding treatment for the affected family members. We performed NGS in a panel of 600 genes for blood diseases on a patient with obscure hemolytic anemia and her parents. We confirmed the diagnosis of pyruvate kinase deficiency, identified a novel homozygous mutation of the PKLR gene (NM_000298: exon 6: c.T941C: p.I314T), and ruled out other blood diseases in the Chinese family. Furthermore, amniotic fluid was taken from the mother during the second trimester, and DNA was extracted to analyze the type of PKLR gene mutation...
January 18, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29349655/total-body-irradiation-tremendously-impair-the-proliferation-differentiation-and-chromosomal-integrity-of-bone-marrow-derived-mesenchymal-stromal-stem-cells
#16
Wen-Jyi Lo, Chiao-Lin Lin, Yu-Chien Chang, Li-Yuan Bai, Chen-Yuan Lin, Ji-An Liang, Long-Yuan Li, Ling-Min Chao, Chang-Fang Chiu, Chuan-Mu Chen, Su-Peng Yeh
Total body irradiation (TBI) is frequently used in hematopoietic stem cell transplantation (HSCT) and is associated with many complications due to radiation injury to the normal cells, including normal stem cells. Nevertheless, the effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical to that used in TBI-conditioning HSCT. The characteristics, differentiation potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity of the irradiated BM-MSCs were then compared to the non-irradiated control...
January 18, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29348885/drug-resistance-in-doxorubicin-resistant-fl5-12-hematopoietic-cells-elevated-mdr1-drug-efflux-and-side-population-positive-and-decreased-bcl2-family-member-expression
#17
Linda S Steelman, Steve L Abrams, Peter Ruvolo, Vivian Ruvolo, Lucio Cocco, Stefano Ratti, Alberto M Martelli, Luca M Neri, Saverio Candido, Massimo Libra, James A McCubrey
Chemotherapeutic drug treatment can result in the emergence of drug-resistant cells. By culturing an interleukin-3 (IL-3)-dependent cell line, FL5.12 cells in the presence of the chemotherapeutic drug doxorubicin, we isolated FL/Doxo cells which are multi-drug resistant. Increased levels of drug efflux were detected in FL/Doxo cells which could be inhibited by the MDR1 inhibitor verapamil but not by the MRP1 inhibitor MK571. The effects of TP53 and MEK1 were examined by infection of FL/Doxo cells with retroviruses encoding either a dominant negative TP-53 gene (FL/Doxo+ TP53 (DN) or a constitutively-activated MEK-1 gene (FL/Doxo + MEK1 (CA)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348881/allogeneic-stem-cell-transplantation-in-acute-lymphoblastic-leukemia-patients-older-than-60-years-a-survey-from-the-acute-leukemia-working-party-of-ebmt
#18
Gabrielle Roth-Guepin, Jonathan Canaani, Annalisa Ruggeri, Myriam Labopin, Juergen Finke, Jan J Cornelissen, Jeremy Delage, Gernot Stuhler, Monserrat Rovira, Mike Potter, Michael Stadler, Hendrik Veelken, Jean Yves Cahn, Matthew Collin, Yves Beguin, Sebastian Giebel, Arnon Nagler, Mohamad Mohty
Hematopoietic stem cell transplantation (HSCT) is being increasingly explored as a treatment modality for older patients with acute lymphoblastic leukemia (ALL). Yet, concerns regarding the long term outcome of transplantation in older patients limit the wide spread applicability of this approach. In this analysis we set out to determine the outcome of ALL patients over the age of 60 who underwent reduced intensity HSCT. Herein, we present the experience of the acute leukemia working party (ALWP) of the EBMT in this age group...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348130/setd1a-protects-hscs-from-activation-induced-functional-decline-in-vivo
#19
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/29346763/derepression-of-the-iroquois-homeodomain-transcription-factor-gene-irx3-confers-differentiation-block-in-acute-leukemia
#20
Tim D D Somerville, Fabrizio Simeoni, John A Chadwick, Emma L Williams, Gary J Spencer, Katalin Boros, Christopher Wirth, Eleni Tholouli, Richard J Byers, Tim C P Somervaille
The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML), ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression...
January 16, 2018: Cell Reports
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