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stem cell disease modelling

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https://www.readbyqxmd.com/read/28453285/pharmacological-reprogramming-of-somatic-cells-for-regenerative-medicine
#1
Min Xie, Shibing Tang, Ke Li, Sheng Ding
Lost or damaged cells in tissues and organs can be replaced by transplanting therapeutically competent cells. This approach requires methods that effectively manipulate cellular identities and properties to generate sufficient numbers of desired cell types for transplantation. These cells can be generated by reprogramming readily available somatic cells, such as fibroblasts, into induced pluripotent stem cells (iPSCs), which can replicate indefinitely and give rise to any somatic cell type. This reprogramming can be achieved with genetic methods, such as forced expression of pluripotency-inducing transcription factors (TFs), which can be further improved, or even avoided, with pharmacological agents...
April 28, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28447889/bone-marrow-as-a-hematopoietic-stem-cell-source-for-gene-therapy-in-sickle-cell-disease-scd-evidence-from-rhesus-and-scd-patients
#2
Naoya Uchida, Atsushi Fujita, Matthew M Hsieh, Aylin Bonifacino, Allen E Krouse, Mark E Metzger, Robert E Donahue, John F Tisdale
Steady state bone marrow (BM) is the preferred hematopoietic stem cell (HSC) source for gene therapy in sickle cell disease (SCD) due to the recognized risk of vaso-occlusive crisis during granulocyte colony-stimulating factor mobilization. We previously established clinically relevant HSC gene transfer in the rhesus model following transplantation of mobilized peripheral blood (PB) CD34+ cells transduced with lentiviral vectors. In this study, we examined steady state bone marrow (BM) in the rhesus competitive repopulation model and demonstrate similar gene marking in vitro and in vivo, as compared to mobilized PB CD34+ cells...
April 27, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28447035/novel-therapeutic-approaches-rett-syndrome-and-human-induced-pluripotent-stem-cell-technology
#3
REVIEW
Mohan Gomathi, Vellingiri Balachandar
Recent advances in induced pluripotent stem cell (iPSC) technology target screening and discovering of therapeutic agents for the possible cure of human diseases. Human induced pluripotent stem cells (hiPSC) are the right kind of platform for testing potency of specific active compounds. Ayurveda, the Indian traditional system of medicine developed between 2,500 and 500 BC, is a science involving the intelligent formulations of herbs and minerals. It can serve as a "goldmine" for novel neuroprotective agents used for centuries to treat neurological disorders...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28446779/functional-neuronal-differentiation-of-injury-induced-muscle-derived-stem-cell-like-cells-with-therapeutic-implications
#4
Kinga Vojnits, Haiying Pan, Xiaojing Dai, Hao Sun, Qingchun Tong, Radbod Darabi, Johnny Huard, Yong Li
Mammalian skeletal muscles contain a number of heterogeneous cell populations. Our previous study characterized a unique population of myogenic lineage stem cells that can be isolated from adult mammalian skeletal muscles upon injury. These injury-induced muscle-derived stem cell-like cells (iMuSCs) displayed a multipotent state with sensitiveness and strong migration abilities. Here, we report that these iMuSCs have the capability to form neurospheres that represent multiple neural phenotypes. The induced neuronal cells expressed various neuron-specific proteins, their mRNA expression during neuronal differentiation recapitulated embryonic neurogenesis, they generated action potentials, and they formed functional synapses in vitro...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28446286/-salvage-trerapy-for-patients-with-relapsed-and-refractory-lymphoma-by-allogeneic-hematopoietic-stem-cell-transplantation
#5
Yue Yin, Zhi-Xiang Qiu, Yuan Li, Wei-Lin Xu, Yu-Hua Sun, Wei Liu, Wen-Sheng Wang, Mang-Ju Wang, Li-Hong Wang, Yu-Jun Dong, Jin-Ping Ou, Xi-Nan Cen, Han-Yun Ren
OBJECTIVE: To assess the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treating patients with relapsed and refractory lymphoma. METHODS: Thirty-one consecutive patients with relapsed or refractory lymphoma received allo-HSCT. Used conditioning regimens included conditioning based on BEAM regimen(12 cases), conditioning based on modified Bu/Cy regimen(11 cases), conditioning based on Cy/TBI regemen(6 cases) and conditioning of Bu/Cy regimen(1 case)...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446249/adipose-derived-mesenchymal-stem-cells-modulate-cd14-cd16-expression-on-monocytes-from-sepsis-patients-in-vitro-via-prostaglandin-e2
#6
Guanguan Qiu, Guoping Zheng, Menghua Ge, Lanfang Huang, Haijiang Tong, Ping Chen, Dengming Lai, Yaoqin Hu, Baoli Cheng, Qiang Shu, Jianguo Xu
BACKGROUND: Mesenchymal stem cells (MSCs) have been shown to reduce sepsis-induced inflammation and improve survival in mouse models of sepsis. CD16(+) monocytes are proinflammatory and abundant in inflammatory conditions such as sepsis. The primary objective in this exploratory study was to determine the effects of adipose-derived MSCs (ASCs) on three subsets of monocytes from sepsis patients in vitro and to delineate the underlying mechanism. METHODS: This is a prospective cohort study of patients admitted to the medical intensive care unit (ICU) at an academic medical center...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28445516/transplantation-of-induced-mesenchymal-stem-cells-for-treating-chronic-renal-insufficiency
#7
Xing-Hua Pan, Jing Zhou, Xiang Yao, Jun Shu, Ju-Fen Liu, Jian-Yong Yang, Rong-Qing Pang, Guang-Ping Ruan
Discovering a new cell transplantation approach for treating chronic renal insufficiency is a goal of many nephrologists. In vitro-cultured peripheral blood mononuclear cells (PBMCs) were reprogrammed into induced mesenchymal stem cells (iMSCs) by using natural inducing agents made in our laboratory. The stem cell phenotype of the iMSCs was then identified. Unilateral ureteral obstruction (UUO) was used to create an animal model of chronic renal insufficiency characterized by renal interstitial fibrosis. The induced and non-induced PBMCs were transplanted, and the efficacy of iMSCs in treating chronic renal insufficiency was evaluated using a variety of methods...
2017: PloS One
https://www.readbyqxmd.com/read/28445465/assembly-of-functionally-integrated-human-forebrain-spheroids
#8
Fikri Birey, Jimena Andersen, Christopher D Makinson, Saiful Islam, Wu Wei, Nina Huber, H Christina Fan, Kimberly R Cordes Metzler, Georgia Panagiotakos, Nicholas Thom, Nancy A O'Rourke, Lars M Steinmetz, Jonathan A Bernstein, Joachim Hallmayer, John R Huguenard, Sergiu P Paşca
The development of the nervous system involves a coordinated succession of events including the migration of GABAergic (γ-aminobutyric-acid-releasing) neurons from ventral to dorsal forebrain and their integration into cortical circuits. However, these interregional interactions have not yet been modelled with human cells. Here we generate three-dimensional spheroids from human pluripotent stem cells that resemble either the dorsal or ventral forebrain and contain cortical glutamatergic or GABAergic neurons...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28444230/apoe-%C3%AE%C2%B54-%C3%AE%C2%B54-diminishes-neurotrophic-function-of-human-ipsc-derived-astrocytes
#9
Jing Zhao, Mary D Davis, Yuka Atagi, Mitsuru Shinohara, Neill R Graff-Radford, Steven G Younkin, Zbigniew K Wszolek, Takahisa Kanekiyo, Guojun Bu
The ε4 allele of the APOE gene encoding apolipoprotein E (apoE) is a strong genetic risk factor for aging-related cognitive decline as well as late-onset Alzheimer's disease (AD) compared to the common ε3 allele. In the central nervous system, apoE is produced primarily by astrocytes and functions in transporting lipids including cholesterol to support neuronal homeostasis and synaptic integrity. Although mouse models and corresponding primary cells have provided valuable tools for studying apoE isoform-dependent functions, recent studies have shown that human astrocytes have distinct gene expression profile compare with rodent astrocytes...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28444193/quantitative-assessment-of-timing-efficiency-specificity-and-genetic-mosaicism-of-crispr-cas9-mediated-gene-editing-of-hemoglobin-beta-gene-in-rhesus-monkey-embryos
#10
Uros Midic, Pei-Hsuan Hung, Kailey A Vincent, Benjamin Goheen, Patrick G Schupp, Diane D Chen, Daniel E Bauer, Catherine A VandeVoort, Keith E Latham
Gene editing technologies offer new options for developing novel biomedical research models and for gene and stem cell based therapies. However, applications in many species demand high efficiencies, specificity, and a thorough understanding of likely editing outcomes. To date, overall efficiencies, rates of off-targeting, and degree of genetic mosaicism have not been well-characterized for most species, limiting our ability to optimize methods. As a model gene for measuring these parameters of CRISPR/Cas9 application in a primate species (rhesus monkey), we selected the β-hemoglobin gene (HBB), which also has high relevance to potential application of gene editing and stem-cell technologies for treating human disease...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28440472/human-umbilical-cord-mesenchymal-stem-cells-alleviate-acute-myocarditis-by-modulating-endoplasmic-reticulum-stress-and-extracellular-signal-regulated-1-2-mediated-apoptosis
#11
Changyi Zhang, Guichi Zhou, Chanxin Cai, Jindi Li, Fen Chen, Lichun Xie, Wei Wang, Yonggang Zhang, Xiulan Lai, Lian Ma
Acute myocarditis is a non-ischemic inflammatory disease of the myocardium, and there is currently no standard treatment. Mesenchymal stem cells (MSCs) can alleviate myosin‑induced myocarditis; however, the mechanism has not been clearly elucidated. In the present study, the authors investigated the ability of human umbilical cordMSCs (HuMSCs) to attenuate myocardial injury and dysfunction during the acute phase of experimental myocarditis. Male Lewis rats (aged 8 weeks) were injected with porcine myosin to induce myocarditis...
April 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440309/glypican-2-levels-in-cerebrospinal-fluid-predict-the-status-of-adult-hippocampal-neurogenesis
#12
S Lugert, T Kremer, R Jagasia, A Herrmann, S Aigner, C Giachino, I Mendez-David, A M Gardier, J P Carralot, H Meistermann, A Augustin, M D Saxe, J Lamerz, G Duran-Pacheco, A Ducret, V Taylor, D J David, C Czech
Adult hippocampal neurogenesis is a remarkable form of brain plasticity through which new neurons are generated throughout life. Despite its important roles in cognition and emotion and its modulation in various preclinical disease models, the functional importance of adult hippocampal neurogenesis in human health has not been revealed because of a lack of tools for monitoring adult neurogenesis in vivo. Therefore, we performed an unbiased proteomics screen to identify novel proteins expressed during neuronal differentiation using a human neural stem cell model, and we identified the proteoglycan Glypican-2 (Gpc2) as a putative secreted marker of immature neurons...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439558/crispr-cpf1-correction-of-muscular-dystrophy-mutations-in-human-cardiomyocytes-and-mice
#13
Yu Zhang, Chengzu Long, Hui Li, John R McAnally, Kedryn K Baskin, John M Shelton, Rhonda Bassel-Duby, Eric N Olson
Duchenne muscular dystrophy (DMD), caused by mutations in the X-linked dystrophin gene (DMD), is characterized by fatal degeneration of striated muscles. Dilated cardiomyopathy is one of the most common lethal features of the disease. We deployed Cpf1, a unique class 2 CRISPR (clustered regularly interspaced short palindromic repeats) effector, to correct DMD mutations in patient-derived induced pluripotent stem cells (iPSCs) and mdx mice, an animal model of DMD. Cpf1-mediated genomic editing of human iPSCs, either by skipping of an out-of-frame DMD exon or by correcting a nonsense mutation, restored dystrophin expression after differentiation to cardiomyocytes and enhanced contractile function...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28439518/diabetes-adult-neurogenesis-and-brain-remodeling-new-insights-from-rodent-and-zebrafish-models
#14
REVIEW
Anne-Claire Dorsemans, David Couret, Anaïs Hoarau, Olivier Meilhac, Christian Lefebvre d'Hellencourt, Nicolas Diotel
The prevalence of diabetes rapidly increased during the last decades in association with important changes in lifestyle. Diabetes and hyperglycemia are well-known for inducing deleterious effects on physiologic processes, increasing for instance cardiovascular diseases, nephropathy, retinopathy and foot ulceration. Interestingly, diabetes also impairs brain morphology and functions such as (1) decreased neurogenesis (proliferation, differentiation and cell survival), (2) decreased brain volumes, (3) increased blood-brain barrier leakage, (4) increased cognitive impairments, as well as (5) increased stroke incidence and worse neurologic outcomes following stroke...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28438184/microbiota-activated-cd103-dcs-stemming-from-microbiota-adaptation-specifically-drive-%C3%AE-%C3%AE-t17-proliferation-and-activation
#15
Chris Fleming, Yihua Cai, Xuan Sun, Venkatakrishna R Jala, Feng Xue, Samantha Morrissey, Yu-Ling Wei, Yueh-Hsiu Chien, Huang-Ge Zhang, Bodduluri Haribabu, Jian Huang, Jun Yan
BACKGROUND: IL-17-producing γδT cells (γδT17) promote autoinflammatory diseases and cancers. Yet, γδT17 peripheral regulation has not been thoroughly explored especially in the context of microbiota-host interaction. The potent antigen-presenting CD103(+) dendritic cell (DC) is a key immune player in close contact with both γδT17 cells and microbiota. This study presents a novel cellular network among microbiota, CD103(+) DCs, and γδT17 cells. METHODS: Immunophenotyping of IL-17r(-/-) mice and IL-17r(-/-) IRF8(-/-) mice were performed by ex vivo immunostaining and flow cytometric analysis...
April 24, 2017: Microbiome
https://www.readbyqxmd.com/read/28436965/a-three-dimensional-model-of-human-lung-development-and-disease-from-pluripotent-stem-cells
#16
Ya-Wen Chen, Sarah Xuelian Huang, Ana Luisa Rodrigues Toste de Carvalho, Siu-Hong Ho, Mohammad Naimul Islam, Stefano Volpi, Luigi D Notarangelo, Michael Ciancanelli, Jean-Laurent Casanova, Jahar Bhattacharya, Alice F Liang, Laura M Palermo, Matteo Porotto, Anne Moscona, Hans-Willem Snoeck
Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28434074/adipose-derived-stem-cells-ameliorate-experimental-murine-colitis-via-tsp-1-dependent-activation-of-latent-tgf-%C3%AE
#17
Hiroshi Takeyama, Tsunekazu Mizushima, Mamoru Uemura, Naotsugu Haraguchi, Junichi Nishimura, Taishi Hata, Chu Matsuda, Ichiro Takemasa, Masakazu Ikenaga, Kohei Murata, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori
BACKGROUND: Adipose tissue-derived stem cells (ASCs) have been investigated as therapeutic tools for a variety of autoimmune diseases, including inflammatory diseases. However, the mechanisms underlying the immunomodulatory properties of ASCs are not well understood. Here, we investigated the mechanism of regulatory T cell (Treg) induction in ASC therapy in a murine model of inflammatory bowel disease. METHODS: Acute colitis was induced in mice using dextran sulfate sodium and ASCs administered intraperitoneally...
April 22, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28433939/enhanced-proangiogenic-potential-of-mesenchymal-stem-cell-derived-exosomes-stimulated-by-a-nitric-oxide-releasing-polymer
#18
Wei Du, Kaiyue Zhang, Shuaiqiang Zhang, Ran Wang, Yan Nie, Hongyan Tao, Zhibo Han, Lu Liang, Di Wang, Jianfeng Liu, Na Liu, Zhongchao Han, Deling Kong, Qiang Zhao, Zongjin Li
Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for the treatment of degenerative diseases or injury and may provide an alternative to cell-based therapy. However, the compositions in MSC-derived exosomes are highly influenced by the microenvironment in which their original cells reside. Here, we hypothesized that a nitric oxide (NO)-releasing polymer can boost the proangiogenic compositions of exosomes and enhance their proangiogenic capacity. Our results demonstrated that exosomes, released from human placenta-derived MSCs (hP-MSCs) by NO stimulation, augment the angiogenic effects of human umbilical vein endothelial cells (HUVECs) in vitro...
April 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28432872/human-effector-memory-t-helper-cells-engage-with-mouse-macrophages-and-cause-graft-versus-host-like-pathology-in-skin-of-humanized-mice-used-in-a-nonclinical-immunization-study
#19
Bala S Sundarasetty, Valery Volk, Sebastian J Theobald, Susanne Rittinghausen, Dirk Schaudien, Vanessa Neuhaus, Constanca Figueiredo, Andreas Schneider, Laura Gerasch, Adele Mucci, Thomas Moritz, Constantin von Kaisenberg, Loukia M Spineli, Katherina Sewald, Armin Braun, Henning Weigt, Arnold Ganser, Renata Stripecke
Humanized mice engrafted with human hematopoietic stem cells and developing functional human T-cell adaptive responses are in critical demand to test human-specific therapeutics. We previously showed that humanized mice immunized with long-lived induced-dendritic cells loaded with the pp65 viral antigen (iDCpp65) exhibited a faster development and maturation of T cells. Herein, we evaluated these effects in a long-term (36 weeks) nonclinical model using two stem cell donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization boosted the output of effector memory CD4(+) T cells in peripheral blood and lymph nodes...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28432220/mir-155-promotes-flt3-itd-induced-myeloproliferative-disease-through-inhibition-of-the-interferon-response
#20
Jared A Wallace, Dominique A Kagele, Anna M Eiring, Carissa N Kim, Ruozhen Hu, Marah C Runtsch, Margaret Alexander, Thomas B Huffaker, Soh-Hyun Lee, Ami B Patel, Timothy L Mosbruger, Warren Voth, Dinesh S Rao, Rodney R Miles, June L Round, Michael W Deininger, Ryan M O'Connell
FLT3-ITD(+) AML accounts for approximately 25% of all AML cases, and is a subtype that carries a poor prognosis. miR-155 is specifically overexpressed in FLT3-ITD(+) AML compared to FLT3-WT AML, and is critical for the growth of FLT3-ITD(+) AML cells in vitro. However, miR-155's role in regulating FLT3-ITD-mediated disease in vivo remains unclear. In this study, we utilized a genetic mouse model to determine whether miR-155 influences the development of FLT3-ITD-induced myeloproliferative disease. Results indicate that miR-155 promotes FLT3-ITD-induced myeloid expansion in the bone marrow, spleen, and peripheral blood...
April 21, 2017: Blood
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