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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
#1
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: Risk assessment of chronic cardiac safety liabilities within the pharmaceutical industry is mostly performed during late stages of pre-clinical 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 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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 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...
December 16, 2016: 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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/27822310/anaphylactic-shock-during-cement-implantation-of-a-total-hip-arthroplasty-in-a-patient-with-underlying-mastocytosis-case-report-of-a-rare-intraoperative-complication
#11
Anita Ten Hagen, Pieter Doldersum, Tom van Raaij
BACKGROUND: Cemented total hip arthroplasty (THA) is a safe and common procedure. In rare cases life threatening bone cement implantation syndrome (BCIS) may occur, which is commonly caused by pulmonary embolism (PE). CASE PRESENTATION: We describe the rare case of a 70-year old patient who underwent an elective total hip replacement. Before surgery he was diagnosed with underlying systemic indolent mastocytosis, a rare pathological disorder that may result in anaphylaxis after massive systemic mast cell activation...
2016: Patient Safety in Surgery
https://www.readbyqxmd.com/read/27803113/histopathological-evaluation-and-expression-of-the-pluripotent-mesenchymal-stem-cell-like-markers-cd105-and-cd44-in-the-synovial-membrane-of-patients-with-primary-versus-secondary-hip-osteoarthritis
#12
Sabin Gligore Turdean, Ioan Jung, Simona Gurzu, Ancuta Zazgyva, Annamaria Fetyko, Ciprian Oliviu Roman, Mihai Turcu, Tudor Sorin Pop
To present the morphological changes of classic primary versus rapidly progressive and secondary hip osteoarthritis (HO) and to examine the expression of two pluripotent mesenchymal stem cell-like markers in the synovial membrane. A prospective observational study was conducted in 57 consecutive cases of radiologically confirmed HO in which total hip arthroplasty was performed. Based on the radiological and clinicopathological features, the cases were divided into three categories: classic primary HO (group A; n=16), rapidly destructive HO (group B; n=24), and HO secondary to avascular osteonecrosis of the femoral head (group C; n=17)...
November 1, 2016: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/27786288/an-inhibitor-of-fibroblast-growth-factor-receptor-1-fgfr1-promotes-late-stage-terminal-differentiation-from-ngn3-pancreatic-endocrine-progenitors
#13
Yzumi Yamashita-Sugahara, Masahito Matsumoto, Manami Ohtaka, Ken Nishimura, Mahito Nakanishi, Kohnosuke Mitani, Yasushi Okazaki
Human induced pluripotent stem cells (hiPSCs) provide a potential resource for regenerative medicine. To identify the signalling pathway(s) contributing to the development of functional β cells, we established a tracing model consisting of dual knock-in hiPSCs (INS-Venus/NGN3-mCherry) (hIveNry) expressing the fluorescent proteins Venus and mCherry under the control of intrinsic insulin (INS) and neurogenin 3 (NGN3) promoters, respectively. hIveNry iPSCs differentiated into NGN3- and mCherry-positive endocrine progenitors and then into Venus-positive β cells expressing INS, PDX1, NKX6...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27762664/limited-immunogenicity-of-human-induced-pluripotent-stem-cell-derived-cartilages
#14
Takeshi Kimura, Akihiro Yamashita, Keiichi Ozono, Noriyuki Tsumaki
Articular cartilage damage does not spontaneously heal and could ultimately result in a loss of joint function. Damaged cartilage can be repaired with cell/tissue sources that are transplanted, however, autologous chondrocytes are limited in number as a cell source. Induced pluripotent stem cells (iPSCs) are a relatively new and abundant cell source and can be made from the patient, but at a considerable cost. Because cartilage is immunoprivileged tissue, allogeneic cartilages have been transplanted effectively without matching for human leukocyte antigen (HLA), but are difficult to acquire due to scarcity of donors...
December 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27717361/effect-of-intraarticular-inoculation-of-mesenchymal-stem-cells-in-dogs-with-hip-osteoarthritis-by-means-of-objective-force-platform-gait-analysis-concordance-with-numeric-subjective-scoring-scales
#15
Jose M Vilar, Belen Cuervo, Monica Rubio, Joaquín Sopena, Juan M Domínguez, Angelo Santana, Jose M Carrillo
BACKGROUND: Subjective pain assessment scales have been widely used for assessing lameness in response to pain, but the accuracy of these scales has been questioned. To assess scale accuracy, 10 lame, presa Canario dogs with osteoarthritis (OA) associated with bilateral hip dysplasia were first treated with mesenchymal stem cells. Then, potential lameness improvement was analyzed using two pain scales (Bioarth and visual analog scale). These data were compared with similar data collected using a force platform with the same animals during a period of 6 months after treatment...
October 7, 2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27703173/risk-of-prenatal-depression-and-stress-treatment-alteration-on-serotonin-system-of-offspring-through-exposure-to-fluoxetine
#16
Siran Pei, Li Liu, Zhaomin Zhong, Han Wang, Shuo Lin, Jing Shang
Fluoxetine is widely used to treat depression, including depression in pregnant and postpartum women. Studies suggest that fluoxetine may have adverse effects on offspring, presumably through its action on various serotonin receptors (HTRs). However, definitive evidence and the underlying mechanisms are largely unavailable. As initial steps towards establishing a human cellular and animal model, we analyzed the expression patterns of several HTRs through the differentiation of human induced pluripotent stem (hiPS) cells into neuronal cells, and analyzed expression pattern in zebrafish embryos...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27650895/exosomes-tricalcium-phosphate-combination-scaffolds-can-enhance-bone-regeneration-by-activating-the-pi3k-akt-signaling-pathway
#17
Jieyuan Zhang, Xiaolin Liu, Haiyan Li, Chunyuan Chen, Bin Hu, Xin Niu, Qing Li, Bizeng Zhao, Zongping Xie, Yang Wang
BACKGROUND: Recently, accumulating evidence has shown that exosomes, the naturally secreted nanocarriers of cells, can exert therapeutic effects in various disease models in the absence of parent cells. However, application of exosomes in bone defect repair and regeneration has been rarely reported, and little is known regarding their underlying mechanisms. METHODS: Exosomes derived from human-induced pluripotent stem cell-derived mesenchymal stem cells (hiPS-MSC-Exos) were combined with tricalcium phosphate (β-TCP) to repair critical-sized calvarial bone defects, and the efficacy was assessed by histological examination...
September 20, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27646297/comprehensive-in-vitro-cardiac-safety-assessment-using-human-stem-cell-technology-overview-of-csahi-heart-initiative
#18
REVIEW
Kiyoshi Takasuna, Keiichi Asakura, Seiichi Araki, Hiroyuki Ando, Katsuyuki Kazusa, Takashi Kitaguchi, Takeshi Kunimatsu, Shinobu Suzuki, Norimasa Miyamoto
Recent increasing evidence suggests that the currently-used platforms in vitro IKr and APD, and/or in vivo QT assays are not fully predictive for TdP, and do not address potential arrhythmia (VT and/or VF) induced by diverse mechanisms of action. In addition, other cardiac safety liabilities such as functional dysfunction of excitation-contraction coupling (contractility) and structural damage (morphological damage to cardiomyocytes) are also major causes of drug attrition, but current in vitro assays do not cover all these liabilities...
January 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27639333/gelatin-scaffold-combined-with-bone-morphogenetic-protein-4-induces-odontoblast-like-cell-differentiation-involving-integrin-profile-changes-autophagy-related-gene-10-and-wnt5-sequentially-in-human-induced-pluripotent-stem-cells
#19
Nobuaki Ozeki, Naoko Hase, Naoya Higuchi, Taiki Hiyama, Hideyuki Yamaguchi, Rie Kawai, Toru Matsumoto, Kazuhiko Nakata, Makio Mogi
While human induced pluripotent stem (hiPS) cells have potential use in regenerative medicine, there are no reports on odontoblastic differentiation of hiPS cells. In the current study, to examine integrin profiles and explore the early signaling cascade of odontoblastic differentiation in hiPS cells, we investigated the regulation of autophagy-related gene (Atg) and wingless/int1 (Wnt) signaling in gelatin scaffold (GS) combined with bone morphogenetic protein (BMP)-4 (GS/BMP-4)-mediated odontoblastic differentiation...
September 15, 2016: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/27638920/generation-of-human-induced-pluripotent-stem-cell-derived-bona-fide-neural-stem-cells-for-ex-vivo-gene-therapy-of-metachromatic-leukodystrophy
#20
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...
September 16, 2016: Stem Cells Translational Medicine
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