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https://www.readbyqxmd.com/read/29053791/pharmacological-targeting-of-apelin-impairs-glioblastoma-growth
#1
Elizabeth Harford-Wright, Gwennan Andre-Gregoire, Kathryn A Jacobs, Lucas Treps, Sophie Le Gonidec, Heloise M Leclair, Sara Gonzalez-Diest, Quentin Roux, François Guillonneau, Delphine Loussouarn, Lisa Oliver, François M Vallette, Fabienne Foufelle, Philippe Valet, Anthony P Davenport, Robert C Glen, Nicolas Bidere, Julie Gavard
Glioblastoma are highly aggressive brain tumours that are associated with an extremely poor prognosis. Within these tumours exists a subpopulation of highly plastic self-renewing cancer cells that retain the ability to expand ex vivo as tumourspheres, induce tumour growth in mice, and have been implicated in radio- and chemo-resistance. Although their identity and fate are regulated by external cues emanating from endothelial cells, the nature of such signals remains unknown. Here, we used a mass spectrometry proteomic approach to characterize the factors released by brain endothelial cells...
October 3, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29051763/il-12p35-inhibits-neuroinflammation-and-ameliorates-autoimmune-encephalomyelitis
#2
Jin Kyeong Choi, Ivy M Dambuza, Chang He, Cheng-Rong Yu, Anita N Uche, Mary J Mattapallil, Rachel R Caspi, Charles E Egwuagu
Multiple sclerosis (MS) is an inflammatory demyelinating disease in which cytokines produced by immune cells that infiltrate the brain and spinal cord play a central role. We show here that the IL-12p35, the alpha subunit of IL-12 or IL-35 cytokine, might be an effective biologic for suppressing neuroinflammatory responses and ameliorating the pathology of experimental autoimmune encephalomyelitis (EAE), the mouse model of human MS. We further show that IL-12p35 conferred protection from neuropathy by inhibiting the expansion of pathogenic Th17 and Th1 cells and inhibiting trafficking of inflammatory cells into the brain and spinal cord...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29050516/human-bone-marrow-mesenchymal-stromal-cell-derived-osteoblasts-promote-the-expansion-of-hematopoietic-progenitors-through-beta-catenin-and-notch-signaling-pathways
#3
Matthew Michalicka, Gavin Boisjoli, Suria Jahan, Owen Hovey, Emily Doxtator, Ahmad Abu-Khader, Roya Pasha, Nicolas Pineault
Coculture of hematopoietic stem cells (HSC) with primary stromal cells from HSC niches supports the maintenance and expansion of HSC and progenitors ex vivo. However, a major drawback is the availability of primary human samples for research and clinical applications. We investigated the use of in vitro derived osteoblasts as a new source of feeder cells and characterized the molecular pathways that mediate their growth promoting activities. First, we compared the growth and differentiation modulating activities of mesenchymal stromal cells (MSC)-derived osteoblasts (M-OST) to that of their undifferentiated precursor on umbilical cord blood (UCB) progenitors...
October 19, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29050459/third-party-regulatory-t-cells-prevent-murine-acute-graft-versus-host-disease
#4
Jung-Yeon Lim, Keon-Il Im, Yunejin Song, Nayoun Kim, Young-Sun Nam, Young-Woo Jeon, Seok-Goo Cho
Background/Aims: Adoptive therapy with regulatory T (Treg) cells to prevent graft-versus-host disease (GVHD) would benefit from a strategy to improve homing to the sites of inflammation following hematopoietic stem cell transplantation (HSCT). Although donor-derived Treg cells have mainly been used in these models, third-party-derived Treg cells are a promising alternative for cell-based immunotherapy, as they can be screened for pathogens and cell activity, and banked for GVHD prevention...
October 19, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29039064/developments-in-hematopoietic-stem-cell-expansion-and-gene-editing-technologies
#5
Dogacan Yucel, Fatih Kocabas
Hematopoietic stem cells (HSCs) are rare cells, which housed in the adult bone marrow. They maintain all types of differentiated blood cells throughout life. Due to limited availability of HSCs for transplantation, treatment of various inherited bone marrow disorders and anemia requires the development of HSC expansion and gene editing technologies. To this end, various studies addressed the use of cytokines and growth factors for HSC expansion. Major hurdle with these studies was found to be spontaneous differentiation of HSCs into different lineages during ex vivo procedure...
October 17, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29032490/myeloid-derived-suppressor-cells-in-the%C3%A2-tumor-microenvironment-current-knowledge-and-future-perspectives
#6
REVIEW
Maria Ibáñez-Vea, Miren Zuazo, Maria Gato, Hugo Arasanz, Gonzalo Fernández-Hinojal, David Escors, Grazyna Kochan
The current knowledge on tumor-infiltrating myeloid-derived suppressor cells (MDSCs) is based mainly on the extensive work performed in murine models. Data obtained for human counterparts are generated on the basis of tumor analysis from patient samples. Both sources of information led to determination of the main suppressive mechanisms used by these cell subsets in tumor-bearing hosts. As a result of the identification of protein targets responsible for MDSCs suppressive activity, different therapeutics agents have been used to eliminate/reduce their adverse effect...
October 14, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/29030224/transfer-molded-wrappable-microneedle-meshes-for-perivascular-drug-delivery
#7
JiYong Lee, Dae Hyun Kim, Kang Ju Lee, Il Ho Seo, Seung Hyun Park, Eui Hwa Jang, Youngjoo Park, Young-Nam Youn, WonHyoung Ryu
After surgical procedures such as coronary/peripheral bypass grafting or endarterectomy for the treatment of organ ischemia derived from atherosclerosis, intimal hyperplasia (IH) which leads to restenosis or occlusion at the site of graft anastomosis frequently occurs. In order to inhibit IH caused by abnormal growth of smooth muscle cells (SMCs) in tunica media, various perivascular drug delivery devices are reported for delivery of anti-proliferation drugs into vascular tissue. However, there still remain conflicting requirements such as local and unidirectional delivery vs device porosity, and conformal tight device installation vs pulsatile expansion and constriction of blood vessels...
October 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29028071/how-to-isolate-a-ready-to-use-adipose-derived-stem-cells-pellet-for-clinical-application
#8
E Raposio, N Bertozzi
Adipose-derived stem cells (ASCs) are multipotent mesenchymal stem cells (MSCs) that show definitive stem cell characteristics such as plastic adherence in culture, ability to maintain multipotency upon in vitro expansion, and self-renewal capacity. ASCs are particularly promising for use in regenerative medicine because they can be harvested easily from adipose tissue by standard liposuction, with minimal donor site morbidity. Since ASCs do not necessitate ex vivo expansion to obtain clinically significant cell numbers, it is critical to identify a standardized method that maximizes the number of ASCs collected...
September 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28994199/inhibition-of-mek-erk-signalling-pathway-promotes-erythroid-differentiation-and-reduces-hscs-engraftment-in-ex%C3%A2-vivo-expanded-haematopoietic-stem-cells
#9
Morteza Zarrabi, Elaheh Afzal, Mohammad Hossein Asghari, Monireh Mohammad, Hamidreza Aboulkheyr Es, Marzieh Ebrahimi
The MEK/ERK pathway is found to be important in regulating different biological processes such as proliferation, differentiation and survival in a wide variety of cells. However, its role in self-renewal of haematopoietic stem cells is controversial and remains to be clarified. The aim of this study was to understand the role of MEK/ERK pathway in ex vivo expansion of mononuclear cells (MNCs) and purified CD34(+) cells, both derived from human umbilical cord blood (hUCB). Based on our results, culturing the cells in the presence of an inhibitor of MEK/ERK pathway-PD0325901 (PD)-significantly reduces the expansion of CD34(+) and CD34(+)  CD38(-) cells, while there is no change in the expression of stemness-related genes (HOXB4, BMI1)...
October 10, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28988007/chromosome-copy-number-variation-in-telomerized-human-bone-marrow-stromal-cells-insights-for-monitoring-safe-ex-vivo-expansion-of-adult-stem-cells
#10
Jorge S Burns, Linda Harkness, Abdullah Aldahmash, Laurent Gautier, Moustapha Kassem
Adult human bone marrow stromal cells (hBMSC) cultured for cell therapy require evaluation of potency and stability for safe use. Chromosomal aberrations upsetting genomic integrity in such cells have been contrastingly described as "Limited" or "Significant". Previously reported stepwise acquisition of a spontaneous neoplastic phenotype during three-year continuous culture of telomerized cells (hBMSC-TERT20) didn't alter a diploid karyotype measured by spectral karyotype analysis (SKY). Such screening may not adequately monitor abnormal and potentially tumorigenic hBMSC in clinical scenarios...
September 25, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28984359/strategies-to-retain-properties-of-bone-marrow-derived-mesenchymal-stem-cells-ex-vivo
#11
REVIEW
Yaxian Zhou, Tsung-Lin Tsai, Wan-Ju Li
Mesenchymal stem cells (MSCs) have been extensively used for cell therapies and tissue engineering. The current MSC strategy requires a large quantity of cells for such applications, which can be achieved through cell expansion in culture. In the body, stem cell fate is largely determined by their microenvironment, known as the niche. The complex and dynamic stem cell niche provides physical, mechanical, and chemical cues to collaboratively regulate cell activities. It remains a great challenge to maintain the properties of MSCs in culture...
October 6, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28982297/articular-cartilage-repair-with-mesenchymal-stem-cells-after-chondrogenic-priming-a-pilot-study
#12
Troy Bornes, Adetola Adesida, Nadr Jomha
Bone marrow-derived mesenchymal stromal stem cells (BMSCs) are a promising cell source for treating articular cartilage defects. The objective of this study was to assess a protocol that involved autologous transplantation of BMSCs into full-thickness cartilage defects in sheep following isolation, expansion and a short period (4 days) of chondrogenic priming. The impact of oxygen tension during pre-implantation culture was investigated. It was hypothesized that chondrogenically primed BMSCs would produce superior cartilaginous repair tissue relative to control defects, and that culture under hypoxia would yield improved repair tissue in comparison to normoxia...
October 6, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28981121/synthesis-and-characterization-of-well-defined-hydrogel-matrices-and-their-application-to-intestinal-stem-cell-and-organoid-culture
#13
Nikolce Gjorevski, Matthias P Lutolf
Growing cells within an extracellular matrix-like 3D gel is required for, or can improve, the growth of many cell types ex vivo. Here, we describe a protocol for the generation of well-defined matrices for the culture of intestinal stem cells (ISCs) and intestinal organoids. These matrices comprise a poly(ethylene glycol) (PEG) hydrogel backbone functionalized with minimal adhesion cues including RGD (Arg-Gly-Asp), which is sufficient for ISC expansion, and laminin-111, which is required for organoid formation...
November 2017: Nature Protocols
https://www.readbyqxmd.com/read/28980705/empowering-human-cardiac-progenitor-cells-by-p2y14-nucleotide-receptor-overexpression
#14
Farid G Khalafalla, Waqas Kayani, Arwa Kassab, Kelli Ilves, Megan M Monsanto, Roberto Alvarez, Monica Chavarria, Benjamin Norman, Walter P Dembitsky, Mark A Sussman
Autologous cardiac progenitor cell (hCPC) therapy is a promising alternative approach to current inefficient therapies for heart failure (HF). However, ex vivo expansion and pharmacological/genetic modification of hCPCs are necessary interventions to rejuvenate aged/diseased cells and improve their regenerative capacities. This study was designed to assess the potential of improving hCPC functional capacity by targeting P2Y14 purinergic receptor (P2Y14 R), which has been previously reported to induce regenerative and anti-senescence responses in a variety of experimental models...
October 5, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28974254/synergistic-effects-on-mesenchymal-stem-cell-based-cartilage-regeneration-by-chondrogenic-preconditioning-and-mechanical-stimulation
#15
Sien Lin, Wayne Yuk Wai Lee, Qian Feng, Liangliang Xu, Bin Wang, Gene Chi Wai Man, Yuanfeng Chen, Xiaohua Jiang, Liming Bian, Liao Cui, Bo Wei, Gang Li
BACKGROUND: Mesenchymal stem cells (MSCs) hold promising translational potential in cartilage regeneration. However, the efficacy of MSC-based tissue engineering is not satisfactory in the treatment of cartilage defect because of the inevitable cellular functional changes during ex vivo cell expansion. How to maintain the chondrogenic capacity of MSCs to improve their therapeutic outcomes remains an outstanding question. METHODS: Bone marrow-derived MSCs were firstly primed in chondrogenic induction medium which was then replaced with normal growth medium to attain the manipulated cells (M-MSCs)...
October 3, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28972948/a-novel-method-to-induce-cartilage-regeneration-with-cubic-microcartilage
#16
Hitoshi Nishiwaki, Mitsugu Fujita, Makoto Yamauchi, Noritaka Isogai, Yasuhiko Tabata, Hirohisa Kusuhara
Cartilage tissue is characterized by its poor regenerative properties, and the clinical performance of cartilage grafts to replace cartilage defects has been unsatisfactory. Recently, cartilage regeneration with mature chondrocytes and stem cells has been developed and applied in clinical settings. However, there are challenges with the use of mature chondrocytes and stem cells for tissue regeneration, including the high costs associated with the standard stem cell isolation methods and the decreased cell viability due to cell manipulation...
October 4, 2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28968961/critical-role-of-%C3%AE-1-integrin-in-postnatal-beta-cell-function-and-expansion
#17
Jason Peart, Jinming Li, Hojun Lee, Matthew Riopel, Zhi-Chao Feng, Rennian Wang
β1 integrin is essential for pancreatic beta-cell development and maintenance in rodents and humans. However, the effects of a temporal beta-cell specific β1 integrin knockout on adult islet function are unknown. We utilized a mouse insulin 1 promoter driven tamoxifen-inducible Cre-recombinase β1 integrin knockout mouse model (MIPβ1KO) to investigate β1 integrin function in adult pancreatic beta-cells. Adult male MIPβ1KO mice were significantly glucose intolerant due to impaired glucose-stimulated insulin secretion in vivo and ex vivo at 8 weeks post-tamoxifen...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968468/irf-8-regulates-expansion-of-myeloid-derived-suppressor-cells-and-foxp3-regulatory-t-cells-and-modulates-th2-immune-responses-to-gastrointestinal-nematode-infection
#18
Rajesh M Valanparambil, Mifong Tam, Pierre-Paul Gros, Jean-Philippe Auger, Mariela Segura, Philippe Gros, Armando Jardim, Timothy G Geary, Keiko Ozato, Mary M Stevenson
Interferon regulatory factor-8 (IRF-8) is critical for Th1 cell differentiation and negatively regulates myeloid cell development including myeloid-derived suppressor cells (MDSC). MDSC expand during infection with various pathogens including the gastrointestinal (GI) nematode Heligmosomoides polygyrus bakeri (Hpb). We investigated if IRF-8 contributes to Th2 immunity to Hpb infection. Irf8 expression was down-regulated in MDSC from Hpb-infected C57BL/6 (B6) mice. IRF-8 deficient Irf8-/- and BXH-2 mice had significantly higher adult worm burdens than B6 mice after primary or challenge Hpb infection...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28952007/rapid-kv-switching-single-source-dual-energy-ct-ex-vivo-renal-calculi-characterization-using-a-multiparametric-approach-refining-parameters-on-an-expanded-dataset
#19
J Scott Kriegshauser, Robert G Paden, Miao He, Mitchell R Humphreys, Steven I Zell, Yinlin Fu, Teresa Wu, Mark D Sugi, Alvin C Silva
PURPOSE: We aimed to determine the best algorithms for renal stone composition characterization using rapid kV-switching single-source dual-energy computed tomography (rsDECT) and a multiparametric approach after dataset expansion and refinement of variables. METHODS: rsDECT scans (80 and 140 kVp) were performed on 38 ex vivo 5- to 10-mm renal stones composed of uric acid (UA; n = 21), struvite (STR; n = 5), cystine (CYS; n = 5), and calcium oxalate monohydrate (COM; n = 7)...
September 26, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/28941176/optimized-human-platelet-lysate-as-novel-basis-for-a-serum-xeno-and-additive-free-corneal-endothelial-cell-and-tissue-culture
#20
Daniel Thieme, Lynn Reuland, Toni Lindl, Friedrich Kruse, Thomas Fuchsluger
INTRODUCTION: The expansion of donor derived corneal endothelial cells is a promising approach for regenerative therapies in corneal diseases. To achieve the best GMP standard the entire cultivation process should be devoid of non-human components. However, so far there is no suitable xeno-free protocol for clinical applications. METHODS: We therefore introduce a processed variant of a platelet lysate for the use in corneal cell and tissue culture based on a GMP-grade thrombocyte concentrate...
September 21, 2017: Journal of Tissue Engineering and Regenerative Medicine
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