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https://www.readbyqxmd.com/read/28231034/upscaling-of-hips-cell-derived-neurons-for-high-throughput-screening
#1
Stefanie Traub, Heiko Stahl, Holger Rosenbrock, Eric Simon, Ralf Heilker
The advent of human-induced pluripotent stem (hiPS) cell-derived neurons promised to provide better model cells for drug discovery in the context of the central nervous system. This work demonstrates both the upscaling of cellular expansion and the acceleration of neuronal differentiation to accommodate the immense material needs of a high-throughput screening (HTS) approach. Using GRowth factor-driven expansion and INhibition of NotCH (GRINCH) during maturation, the derived cells are here referred to as GRINCH neurons...
March 2017: SLAS Discov
https://www.readbyqxmd.com/read/28191778/generation-of-human-induced-pluripotent-stem-cell-derived-bona-fide-neural-stem-cells-for-ex-vivo-gene-therapy-of-metachromatic-leukodystrophy
#2
Vasco Meneghini, Giacomo Frati, Davide Sala, Silvia De Cicco, Marco Luciani, Chiara Cavazzin, Marianna Paulis, Wieslawa Mentzen, Francesco Morena, Serena Giannelli, Francesca Sanvito, Anna Villa, Alessandro Bulfone, Vania Broccoli, Sabata Martino, Angela Gritti
Allogeneic fetal-derived human neural stem cells (hfNSCs) that are under clinical evaluation for several neurodegenerative diseases display a favorable safety profile, but require immunosuppression upon transplantation in patients. Neural progenitors derived from patient-specific induced pluripotent stem cells (iPSCs) may be relevant for autologous ex vivo gene-therapy applications to treat genetic diseases with unmet medical need. In this scenario, obtaining iPSC-derived neural stem cells (NSCs) showing a reliable "NSC signature" is mandatory...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28174491/comprehensive-evaluation-of-nutritional-status-before-and-after-hematopoietic-stem-cell-transplantation-in-170-patients-with-hematological-diseases
#3
Peng Liu, Boshi Wang, Xia Yan, Jingjing Cai, Yu Wang
OBJECTIVE: To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation (HSCT), and explore optimal methods for assessing nutritional status in patients with hematological diseases. METHODS: This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People's Hospital between May 2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002 (NRS-2002), Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA) and Malnutrition Universal Screening Tools (MUST), in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms...
December 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28159471/microrna-211-and-autophagy-related-gene-14-signaling-regulate-osteoblast-like-cell-differentiation-of-human-induced-pluripotent-stem-cells
#4
Nobuaki Ozeki, Naoko Hase, Taiki Hiyama, Hideyuki Yamaguchi, Rie Kawai-Asano, Kazuhiko Nakata, Makio Mogi
MicroRNAs (miRNAs) have been the subject of recent attention as key regulatory factors in cell differentiation. In the current study, to explore the early signaling cascade of osteogenic differentiation of human induced pluripotent stem (hiPS) cells, we investigated miR-211 regulation and autophagy-related gene (Atg) signaling in osteogenic differentiation. In addition to reciprocal strong induction of miR-211 expression in differentiated cells following osteogenic differentiation, we found abundant Argonaute 3 bound to miR-211⊡ There were also dramatic increases in the mRNA and protein levels of Atg14 together with increases in the amount of autophagosomes as well as autophagic fluxes...
January 31, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28137721/transcriptional-functional-and-mechanistic-comparisons-of-stem-cell-derived-hepatocytes-heparg-cells-and-3d-human-hepatocyte-spheroids-as-predictive-in-vitro-systems-for-drug-induced-liver-injury
#5
Catherine C Bell, Volker M Lauschke, Sabine U Vorrink, Henrik Palmgren, Roger Duffin, Tommy B Andersson, Magnus Ingelman-Sundberg
Reliable and versatile hepatic in vitro systems for the prediction of drug pharmacokinetics and toxicity are essential constituents of preclinical safety assessment pipelines for new medicines. Here, we compared three emerging cell systems, hepatocytes derived from induced pluripotent stem cells (hiPS-Hep), HepaRG cells and 3D primary human hepatocyte (PHH) spheroids at transcriptional and functional levels in a multi-center study to evaluate their potential as predictive models for drug-induced hepatotoxicity...
January 30, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28130552/melatonin-micronutrients-osteopenia-treatment-study-mots-a-translational-study-assessing-melatonin-strontium-citrate-vitamin-d3-and-vitamin-k2-mk7-on-bone-density-bone-marker-turnover-and-health-related-quality-of-life-in-postmenopausal-osteopenic-women-following
#6
Sifat Maria, Mark H Swanson, Larry T Enderby, Frank D'Amico, Brianna Enderby, Rebekah M Samsonraj, Amel Dudakovic, Andre J van Wijnen, Paula A Witt-Enderby
This one-year double blind randomized control trial assessed the effects of nightly melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7; MSDK) on bone mineral density (BMD) and quality of life (QOL) in postmenopausal osteopenic women (ages 49-75). Compared to placebo, MSDK treatment increased BMD in lumbar spine (4.3%) and left femoral neck (2.2%), with an upward trend for total left hip (p=0.069). MSDK increased serum P1NP levels and reduced bone turnover (CTx:P1NP). Psychometric analyses indicated that mood and sleep quality improved for the MSDK group...
January 26, 2017: Aging
https://www.readbyqxmd.com/read/28123640/microrna-410-promotes-chondrogenic-differentiation-of-human-bone-marrow-mesenchymal-stem-cells-through-down-regulating-wnt3a
#7
Yanjie Zhang, Xiaohan Huang, Yanhao Yuan
BACKGROUND: Chondrogenic differentiation of mesenchymal stem cells (MSCs) is important for osteoarthritis (OA) treatment. However, the specific mechanisms involved are undefined. MicroRNAs (miRNAs) downregulate protein synthesis by binding to the 3'UTR of target mRNA. METHODS: Bone marrow aspirates were obtained from OA patients undergoing total hip arthroplasty (n=8) to isolate MSCs. MiR-410 or miR-410 inhibitor were transfected into MSCs using lentivirus and the effects were assessed...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28115945/isolation-and-characterization-of-synovial-mesenchymal-stem-cell-derived-from-hip-joints-a-comparative-analysis-with-a-matched-control-knee-group
#8
Akihisa Hatakeyama, Soshi Uchida, Hajime Utsunomiya, Manabu Tsukamoto, Hirotaka Nakashima, Eiichiro Nakamura, Cecilia Pascual-Garrido, Ichiro Sekiya, Akinori Sakai
Purpose. To determine the characteristics of MSCs from hip and compare them to MSCs from knee. Methods. Synovial tissues were obtained from both the knee and the hip joints in 8 patients who underwent both hip and knee arthroscopies on the same day. MSCs were isolated from the knee and hip synovial samples. The capacities of MSCs were compared between both groups. Results. The number of cells per unit weight at passage 0 of synovium from the knee was significantly higher than that from the hip (P < 0.05)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28114130/identifying-cardiovascular-risk-in-survivors-of-childhood-leukaemia-treated-with-haematopoietic-stem-cell-transplantation-and-total-body-irradiation%C3%A2
#9
Christina Wei, Linda Hunt, Rachel Cox, Karin Bradley, Ruth Elson, Julian Shield, Michael Stevens, Elizabeth Crowne
BACKGROUND: Survivors of childhood with haematopoietic stem cell transplantation and total body irradiation (HSCT/TBI) have an increased cardiometabolic risk without overt obesity. AIM: To describe cardiometabolic risk in HSCT/TBI survivors and identify anthropometric measurements of adiposity representative of cardiometabolic risks in HSCT/TBI survivors. METHOD: Childhood leukaemia survivors treated with HSCT/TBI (n = 21, 11 males) were compared with chemotherapy-only (n = 31) and obese non-leukaemic controls (n = 30)...
January 23, 2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/28107504/sox10-nano-lantern-reporter-human-ips-cells-a-versatile-tool-for-neural-crest-research
#10
Tomoko Horikiri, Hiromi Ohi, Mitsuaki Shibata, Makoto Ikeya, Morio Ueno, Chie Sotozono, Shigeru Kinoshita, Takahiko Sato
The neural crest is a source to produce multipotent neural crest stem cells that have a potential to differentiate into diverse cell types. The transcription factor SOX10 is expressed through early neural crest progenitors and stem cells in vertebrates. Here we report the generation of SOX10-Nano-lantern (NL) reporter human induced pluripotent stem cells (hiPS) by using CRISPR/Cas9 systems, that are beneficial to investigate the generation and maintenance of neural crest progenitor cells. SOX10-NL positive cells are produced transiently from hiPS cells by treatment with TGFβ inhibitor SB431542 and GSK3 inhibitor CHIR99021...
2017: PloS One
https://www.readbyqxmd.com/read/28094846/chronic-drug-induced-effects-on-contractile-motion-properties-and-cardiac-biomarkers-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#11
Ivan Kopljar, An De Bondt, Petra Vinken, Ard Teisman, Bruce Damiano, Nick Goeminne, Ilse Van den Wyngaert, David J Gallacher, Hua Rong Lu
BACKGROUND AND PURPOSE: In the pharmaceutical industry risk assessments of chronic cardiac safety liabilities are mostly performed during late stages of preclinical drug development using in vivo animal models. Here, we explored the potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to detect chronic cardiac risks such as drug-induced cardiomyocyte toxicity. EXPERIMENTAL APPROACH: Video microscopy-based motion field imaging was applied to evaluate the chronic effect (over 72 h) of cardiotoxic drugs on the contractile motion of hiPS-CMs...
January 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28077016/bone-mineral-density-is-close-to-normal-for-age-in-long-term-lymphoma-survivors-treated-with-high-dose-therapy-with-autologous-stem-cell-transplantation
#12
Mette Seland, Knut B Smeland, Trine Bjøro, Ragnhild S Falk, Sophie D Fosså, Clara G Gjesdal, Kristin Godang, Harald Holte, Johan Svartberg, Unni Syversen, Jens Bollerslev, Cecilie E Kiserud
BACKGROUND: Few studies have assessed bone health in lymphoma survivors treated with high-dose therapy with autologous stem cell transplantation (HDT-ASCT). Therefore, we aimed to assess bone mineral density (BMD) at six different skeletal sites and to investigate associations between clinical factors and BMD in these survivors. MATERIAL AND METHODS: Eligible lymphoma survivors were aged ≥18 years at diagnosis and at HDT-ASCT given between 1987 and 2008. Participants responded to questionnaires, blood samples were drawn, and a dual energy X-ray absorptiometry (DXA) was performed...
January 12, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28075482/human-induced-pluripotent-stem-hips-cells-from-urine-samples-a-non-integrative-and-feeder-free-reprogramming-strategy
#13
Clara Steichen, Karim Si-Tayeb, Fanny Wulkan, Thayane Crestani, Graça Rosas, Rafael Dariolli, Alexandre C Pereira, Jose E Krieger
Human induced pluripotent stem (hiPS) cell technology has already revolutionized some aspects of fundamental and applied research such as study of disease mechanisms and pharmacology screening. The first clinical trial using hiPS cell-derived cells began in Japan, only 10 years after the publication of the proof-of concept article. In this exciting context, strategies to generate hiPS cells have evolved quickly, tending towards non-invasive protocols to sample somatic cells combined with "safer" reprogramming strategies...
January 11, 2017: Current Protocols in Human Genetics
https://www.readbyqxmd.com/read/28069985/high-throughput-imaging-of-cardiac-microtissues-for-the-assessment-of-cardiac-contraction-during-drug-discovery
#14
Amy Pointon, James Pilling, Thierry Dorval, Yinhai Wang, Caroline Archer, Christopher Pollard
Cardiotoxicity is a common cause of attrition in preclinical and clinical drug development. Current in vitro approaches have two main limitations, they either are limited to low throughput methods not amendable to drug discovery or lack the physiological responses to allow an integrated risk assessment. A human 3D cardiac microtissue containing human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), cardiac endothelial cells and cardiac fibroblast were used to assess their suitability to detect drug induced changes in cardiomyocyte contraction...
November 15, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28066741/cell-therapy-for-cartilage-defects-of-the-hip
#15
Rodrigo Mardones, Alessio Giai Via, Claudio Jofré, José Minguell, Claudio Rodriguez, Alexander Tomic, Matias Salineros
BACKGROUND: Chondral injuries are commonly related to poor clinical outcome, but recent data showed some improvements in function and pain after hip arthroscopy. Cell-based therapies represent an appealing alternative strategy for cartilage regeneration, and interesting results have been recently reported after intra-articular injections of mesenchymal stem cells (MSCs). The results of hip arthroscopy for femoroacetabular impingement (FAI) and intra-articular injections of autologous expanded bone marrow - MSCs (BM-MSCs) are reported in this retrospective study...
July 2016: Muscles, Ligaments and Tendons Journal
https://www.readbyqxmd.com/read/28018583/ibandronate-for-the-prevention-of-bone-loss-after-allogeneic-stem-cell-transplantation-for-hematologic-malignancies-a-randomized-controlled-trial
#16
Huifang Lu, Richard E Champlin, Uday Popat, Xerxes Pundole, Carmelita P Escalante, Xuemei Wang, Wei Qiao, William A Murphy, Robert F Gagel
The purpose of this study was to evaluate the effects of ibandronate on bone loss following allogeneic stem cell transplantation (allo-SCT). A single-centered, open-label prospective randomized-controlled study following allo-SCT. The treatment group received 3 mg of intravenous ibandronate quarterly starting within 45 days of allo-SCT. All patients received daily calcium and vitamin D supplements. We compared the changes in bone mineral density (BMD) in the lumbar spine, femoral neck and total hip at 6 and 12 months following allo-SCT between the control and treatment groups...
2016: BoneKEy Reports
https://www.readbyqxmd.com/read/27982725/differential-analysis-of-genome-wide-methylation-and-gene-expression-in-mesenchymal-stem-cells-of-patients-with-fractures-and-osteoarthritis
#17
Alvaro Del Real, Flor M Pérez-Campo, Agustín F Fernández, Carolina Sañudo, Carmen G Ibarbia, María I Pérez-Núñez, Wim Van Criekinge, Maarten Braspenning, María A Alonso, Mario F Fraga, Jose A Riancho
Insufficient activity of the bone-forming osteoblasts leads to low bone mass and predisposes to fragility fractures. The functional capacity of human mesenchymal stem cells (hMSCs), the precursors of osteoblasts, may be compromised in elderly individuals, in relation with the epigenetic changes associated with aging. However, the role of hMSCs in the pathogenesis of osteoporosis is still unclear. Therefore, we aimed to characterize the genome-wide methylation and gene expression signatures and the differentiation capacity of hMSCs from patients with hip fractures...
February 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27965712/targeted-inhibition-of-the-mir-199a-214-cluster-by-crispr-interference-augments-the-tumor-tropism-of-human-induced-pluripotent-stem-cell-derived-neural-stem-cells-under-hypoxic-condition
#18
Yumei Luo, Xuehu Xu, Xiuli An, Xiaofang Sun, Shu Wang, Detu Zhu
The human induced pluripotent stem cell (hiPSC) provides a breakthrough approach that helps overcoming ethical and allergenic challenges posed in application of neural stem cells (NSCs) in targeted cancer gene therapy. However, the tumor-tropic capacity of hiPSC-derived NSCs (hiPS-NSCs) still has much room to improve. Here we attempted to promote the tumor tropism of hiPS-NSCs by manipulating the activity of endogenous miR-199a/214 cluster that is involved in regulation of hypoxia-stimulated cell migration...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27906085/tissue-engineered-cardiac-patch-seeded-with-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-promoted-the-regeneration-of-host-cardiomyocytes-in-a-rat-model
#19
Tadahisa Sugiura, Narutoshi Hibino, Christopher K Breuer, Toshiharu Shinoka
BACKGROUND: Thousands of babies are born with congenital heart defects that require surgical repair involving a prosthetic implant. Lack of growth in prosthetic grafts is especially detrimental in pediatric surgery. Cell seeded biodegradable tissue engineered grafts are a novel solution to this problem. The purpose of the present study is to evaluate the feasibility of seeding human induced pluripotent stem cell derived cardiomyocytes (hiPS-CMs) onto a biodegradable cardiac patch. METHODS: The hiPS-CMs were cultured on a biodegradable patch composed of a polyglycolic acid (PGA) and a 50:50 poly (l-lactic-co-ε-caprolactone) copolymer (PLCL) for 1 week...
December 1, 2016: Journal of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/27879223/generation-of-human-induced-pluripotent-stem-cells-in-defined-feeder-free-conditions
#20
Athena Kyrkou, Dimitris Stellas, Marika Syrrou, Apostolos Klinakis, Theodore Fotsis, Carol Murphy
Herein, we describe a modified protocol for the generation of human induced pluripotent stem cells (hiPS) and expansion under defined, serum free and feeder free conditions. These cells exhibit a high level of plasticity towards various differentiation pathways both in vitro and in vivo. Ultimately, hiPS-derived lines achieved high standards of three dimensional differentiations on biomaterial scaffolds and promoted in vivo regeneration of complex organs, such as Anterior Cruciate Ligament (in swine ACL-rupture models) and other tissues as well...
September 2016: Stem Cell Research
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