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https://www.readbyqxmd.com/read/29789652/small-hypoxia-primed-mesenchymal-stem-cells-attenuate-graft-versus-host-disease
#1
YongHwan Kim, Hye Jin Jin, Jinbeom Heo, Hyein Ju, Hye-Yeon Lee, Sujin Kim, Seungun Lee, Jisun Lim, Sang Young Jeong, JiHye Kwon, Miyeon Kim, Soo Jin Choi, Wonil Oh, Yoon Sun Yang, Hyun Ho Hwang, Hwan Yeul Yu, Chae-Min Ryu, Hong Bae Jeon, Dong-Myung Shin
Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation...
May 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29788379/dna-damage-response-and-repair-dna-methylation-and-cell-death-in-human-neurons-and-experimental-animal-neurons-are-different
#2
Lee J Martin, Qing Chang
Neurological disorders affecting individuals in infancy to old age elude interventions for meaningful protection against neurodegeneration, and preclinical work has not translated to humans. We studied human neuron responses to injury and death stimuli compared to those of animal neurons in culture under similar settings of insult (excitotoxicity, oxidative stress, and DNA damage). Human neurons were differentiated from a cortical neuron cell line and the embryonic stem cell-derived H9 line. Mouse neurons were differentiated from forebrain neural stem cells and embryonic cerebral cortex; pig neurons were derived from forebrain neural stem cells...
May 17, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29786565/modelling-non-alcoholic-fatty-liver-disease-in-human-hepatocyte-like-cells
#3
Marcus J Lyall, Jessy Cartier, John P Thomson, Kate Cameron, Jose Meseguer-Ripolles, Eoghan O'Duibhir, Dagmara Szkolnicka, Baltasar Lucendo Villarin, Yu Wang, Giovanny Rodriguez Blanco, Warwick B Dunn, Richard R Meehan, David C Hay, Amanda J Drake
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in developed countries. An in vitro NAFLD model would permit mechanistic studies and enable high-throughput therapeutic screening. While hepatic cancer-derived cell lines are a convenient, renewable resource, their genomic, epigenomic and functional alterations mean their utility in NAFLD modelling is unclear. Additionally, the epigenetic mark 5-hydroxymethylcytosine (5hmC), a cell lineage identifier, is rapidly lost during cell culture, alongside expression of the Ten-eleven-translocation ( TET ) methylcytosine dioxygenase enzymes, restricting meaningful epigenetic analysis...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786556/assessment-of-stem-cell-differentiation-based-on-genome-wide-expression-profiles
#4
REVIEW
Patricio Godoy, Wolfgang Schmidt-Heck, Birte Hellwig, Patrick Nell, David Feuerborn, Jörg Rahnenführer, Kathrin Kattler, Jörn Walter, Nils Blüthgen, Jan G Hengstler
In recent years, protocols have been established to differentiate stem and precursor cells into more mature cell types. However, progress in this field has been hampered by difficulties to assess the differentiation status of stem cell-derived cells in an unbiased manner. Here, we present an analysis pipeline based on published data and methods to quantify the degree of differentiation and to identify transcriptional control factors explaining differences from the intended target cells or tissues. The pipeline requires RNA-Seq or gene array data of the stem cell starting population, derived 'mature' cells and primary target cells or tissue...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786553/from-skeletal-development-to-the-creation-of-pluripotent-stem-cell-derived-bone-forming-progenitors
#5
REVIEW
Wai Long Tam, Frank P Luyten, Scott J Roberts
Bone has many functions. It is responsible for protecting the underlying soft organs, it allows locomotion, houses the bone marrow and stores minerals such as calcium and phosphate. Upon damage, bone tissue can efficiently repair itself. However, healing is hampered if the defect exceeds a critical size and/or is in compromised conditions. The isolation or generation of bone-forming progenitors has applicability to skeletal repair and may be used in tissue engineering approaches. Traditionally, bone engineering uses osteochondrogenic stem cells, which are combined with scaffold materials and growth factors...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786550/generation-of-defined-neural-populations-from-pluripotent-stem-cells
#6
REVIEW
Sarah F McComish, Maeve A Caldwell
Effective and efficient generation of human neural stem cells and subsequently functional neural populations from pluripotent stem cells has facilitated advancements in the study of human development and disease modelling. This review will discuss the established protocols for the generation of defined neural populations including regionalized neurons and astrocytes, oligodendrocytes and microglia. Early protocols were established in embryonic stem cells (ESC) but the discovery of induced pluripotent stem cells (iPSC) in 2006 provided a new platform for modelling human disorders of the central nervous system (CNS)...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786549/pluripotent-stem-cells-induction-and-self-renewal
#7
REVIEW
R Abu-Dawud, N Graffmann, S Ferber, W Wruck, J Adjaye
Pluripotent stem cells (PSCs) lie at the heart of modern regenerative medicine due to their properties of unlimited self-renewal in vitro and their ability to differentiate into cell types representative of the three embryonic germ layers-mesoderm, ectoderm and endoderm. The derivation of induced PSCs bypasses ethical concerns associated with the use of human embryonic stem cells and also enables personalized cell-based therapies. To exploit their regenerative potential, it is essential to have a firm understanding of the molecular processes associated with their induction from somatic cells...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786548/designer-human-tissue-coming-to-a-lab-near-you
#8
David C Hay, Cliona O'Farrelly
Human pluripotent stem cells (PSCs) offer a scalable alternative to primary and transformed human tissue. PSCs include human embryonic stem cells, derived from the inner cell mass of blastocysts unsuitable for human implantation; and induced PSCs, generated by the reprogramming of somatic cells. Both cell types display the ability to self-renew and retain pluripotency, promising an unlimited supply of human somatic cells for biomedical application. A distinct advantage of using PSCs is the ability to select for genetic background, promising personalized modelling of human biology 'in a dish' or immune-matched cell-based therapies for the clinic...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29784997/mechanics-guided-embryonic-patterning-of-neuroectoderm-tissue-from-human-pluripotent-stem-cells
#9
Xufeng Xue, Yubing Sun, Agnes M Resto-Irizarry, Ye Yuan, Koh Meng Aw Yong, Yi Zheng, Shinuo Weng, Yue Shao, Yimin Chai, Lorenz Studer, Jianping Fu
Classic embryological studies have successfully applied genetics and cell biology principles to understand embryonic development. However, it remains unresolved how mechanics, as an integral driver of development, is involved in controlling tissue-scale cell fate patterning. Here we report a micropatterned human pluripotent stem (hPS)-cell-based neuroectoderm developmental model, in which pre-patterned geometrical confinement induces emergent patterning of neuroepithelial and neural plate border cells, mimicking neuroectoderm regionalization during early neurulation in vivo...
May 21, 2018: Nature Materials
https://www.readbyqxmd.com/read/29784672/genetic-screening-and-multipotency-in-rhesus-monkey-haploid-neural-progenitor-cells
#10
Haisong Wang, Wenhao Zhang, Jian Yu, Congyu Wu, Qian Gao, Xu Li, Yanni Li, Jinxin Zhang, Yaru Tian, Tao Tan, Weizhi Ji, Luyuan Li, Yang Yu, Ling Shuai
Haploid embryonic stem cells (haESCs) have been extensively applied in forward and reverse genetic screening. However, the mammalian haploid somatic cell line is difficult to achieve because of spontaneous diploidization in differentiation. As a non-human primate species, monkeys are widely used in basic and pre-clinical research in which haploid cells are restricted to ESCs. Here, we report that rhesus monkey haESCs in an optimized culture medium showed naïve-state pluripotency and stable haploidy. This model facilitated the derivation of haploid neural progenitor cells (haNPCs), which maintained haploidy and differentiation potential into neurons and glia for a long period in vitro High-throughput trapping mutations can be efficiently introduced into haNPCs via piggyBac transposons...
May 21, 2018: Development
https://www.readbyqxmd.com/read/29780042/long-term-culture-of-human-ips-cell-derived-telencephalic-neuron-aggregates-on-collagen-gel
#11
Hiroshi Oyama, Koji Takahashi, Yoshikazu Tanaka, Hiroshi Takemoto, Hisashi Haga
It takes several months to form the 3-dimensional morphology of the human embryonic brain. Therefore, establishing a long-term culture method for neuronal tissues derived from human induced pluripotent stem (iPS) cells is very important for studying human brain development. However, it is difficult to keep primary neurons alive for more than 3 weeks in culture. Moreover, long-term adherent culture to maintain the morphology of telencephalic neuron aggregates induced from human iPS cells is also difficult. Although collagen gel has been widely used to support long-term culture of cells, it is not clear whether human iPS cell-derived neuron aggregates can be cultured for long periods on this substrate...
2018: Cell Structure and Function
https://www.readbyqxmd.com/read/29779899/signaling-dependent-control-of-apical-membrane-size-and-self-renewal-in-rosette-stage-human-neuroepithelial-stem-cells
#12
Jan-Philip Medelnik, Kathleen Roensch, Satoshi Okawa, Antonio Del Sol, Osvaldo Chara, Levan Mchedlishvili, Elly M Tanaka
In the developing nervous system, neural stem cells are polarized and maintain an apical domain facing a central lumen. The presence of apical membrane is thought to have a profound influence on maintaining the stem cell state. With the onset of neurogenesis, cells lose their polarization, and the concomitant loss of the apical domain coincides with a loss of the stem cell identity. Little is known about the molecular signals controlling apical membrane size. Here, we use two neuroepithelial cell systems, one derived from regenerating axolotl spinal cord and the other from human embryonic stem cells, to identify a molecular signaling pathway initiated by lysophosphatidic acid that controls apical membrane size and consequently controls and maintains epithelial organization and lumen size in neuroepithelial rosettes...
May 10, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29779895/identification-and-single-cell-functional-characterization-of-an-endodermally-biased-pluripotent-substate-in-human-embryonic-stem-cells
#13
Thomas F Allison, Andrew J H Smith, Konstantinos Anastassiadis, Jackie Sloane-Stanley, Veronica Biga, Dylan Stavish, James Hackland, Shan Sabri, Justin Langerman, Mark Jones, Kathrin Plath, Daniel Coca, Ivana Barbaric, Paul Gokhale, Peter W Andrews
Human embryonic stem cells (hESCs) display substantial heterogeneity in gene expression, implying the existence of discrete substates within the stem cell compartment. To determine whether these substates impact fate decisions of hESCs we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single-cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long-term self-renewal...
May 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29779043/glis1-3-transcription-factors-critical-roles-in-the-regulation-of-multiple-physiological-processes-and-diseases
#14
REVIEW
Anton M Jetten
Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone biosynthesis, spermatogenesis, and the maintenance of normal kidney functions...
May 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29778975/establishment-of-an-integration-free-induced-pluripotent-stem-cell-line-musii005-a-from-exfoliated-renal-epithelial-cells
#15
Bootsakorn Boonkaew, Weeradee Thummavichit, Ratchapong Netsrithong, Chinnavuth Vatanashevanopakorn, Kovit Pattanapanyasat, Methichit Wattanapanitch
Human induced pluripotent stem cells (iPSCs) were generated from exfoliated renal epithelial cells isolated from a urine sample of a 31-year-old healthy woman. Epithelial cells were characterized for the expression of E-cadherin and reprogrammed using non-integrating Sendai viral vectors. The urine-derived iPSC line (designated as MUSIi005-A) was karyotypically normal, expressed pluripotent markers, differentiated into cells of three embryonic germ layers, and showed no viral and transgene expressions at passage 29...
May 16, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29778974/metabolic-plasticity-during-transition-to-na%C3%A3-ve-like-pluripotency-in-canine-embryo-derived-stem-cells
#16
I C Tobias, R R Isaac, J G Dierolf, R Khazaee, R C Cumming, D H Betts
Pluripotent stem cells (PSCs) have been described in naïve or primed pluripotent states. Domestic dogs are useful translational models in regenerative medicine, but their embryonic stem cells (cESCs) remain narrowly investigated. Primed-like cESCs expanded in the presence of leukemia inhibitory factor and fibroblast growth factor 2 (LIF-FGF2) acquire features of naïve pluripotency when exposed to chemical inhibitors and LIF (2iL). However, proliferation of cESCs is influenced by the pluripotent state and is comparatively slower than human or mouse PSCs...
May 16, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29778942/transcriptomic-and-methylomic-analysis-reveal-the-toxicological-effect-of-2-3-7-8-tetrachlorodibenzodioxin-on-human-embryonic-stem-cell
#17
Keng Po Lai, Jing Woei Li, Ting Fung Chan, Andy Chen, Cherie Yin Lau Lee, William Shu Biu Yeung, Chris Kong Chu Wong
Cumulating epidemiological studies demonstrated that environmental exposure to endocrine disrupting chemicals (EDCs) during the early stages of fetal development is associated with the increase in disease susceptibility in later life. The fetal developmental plasticity is considered as a protective mechanism against an undesirable prenatal environment. Dioxin is one of the environmental contaminants and is considered a diabetogenic factor. Experimental animal and human epidemiological studies have revealed that dioxin exposure was associated with insulin resistance and altered beta cell function...
May 10, 2018: Chemosphere
https://www.readbyqxmd.com/read/29775723/a-scale-out-approach-towards-neural-induction-of-human-induced-pluripotent-stem-cells-for-neurodevelopmental-toxicity-studies
#18
Cláudia C Miranda, Tiago G Fernandes, Sandra N Pinto, Manuel Prieto, M Margarida Diogo, Joaquim M S Cabral
Stem cell's unique properties confer them a multitude of potential applications in the fields of cellular therapy, disease modelling and drug screening fields. In particular, the ability to differentiate neural progenitors (NP) from human induced pluripotent stem cells (hiPSCs) using chemically-defined conditions provides an opportunity to create a simple and straightforward culture platform for application in these fields. Here, we demonstrated that hiPSCs are capable of undergoing neural commitment inside microwells, forming characteristic neural structures resembling neural rosettes and further give rise to glial and neuronal cells...
May 15, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29774076/the-human-somatostatin-receptor-type-2-as-an-imaging-and-suicide-reporter-gene-for-pluripotent-stem-cell-derived-therapy-of-myocardial-infarction
#19
Katrien Neyrinck, Natacha Breuls, Bryan Holvoet, Wouter Oosterlinck, Esther Wolfs, Hubert Vanbilloen, Olivier Gheysens, Robin Duelen, Willy Gsell, Ivo Lambrichts, Uwe Himmelreich, Catherine M Verfaillie, Maurilio Sampaolesi, Christophe M Deroose
Rationale: Pluripotent stem cells (PSCs) are being investigated as a cell source for regenerative medicine since they provide an infinitive pool of cells that are able to differentiate towards every cell type of the body. One possible therapeutic application involves the use of these cells to treat myocardial infarction (MI), a condition where billions of cardiomyocytes (CMs) are lost. Although several protocols have been developed to differentiate PSCs towards CMs, none of these provide a completely pure population, thereby still posing a risk for neoplastic teratoma formation...
2018: Theranostics
https://www.readbyqxmd.com/read/29773904/methanol-fixed-fibroblasts-serve-as-feeder-cells-to-maintain-stem-cells-in-the-pluripotent-state-in-vitro
#20
Yahui Ren, Ziyu Ma, Tong Yu, Min Ling, Huayan Wang
Preparation of mouse embryonic fibroblast (MEF) feeder cells to maintain pluripotent stem cells (PSCs) is time consuming and involved in animal issues. Here, we demonstrated a novel method to prepare feeder cells with high efficiency, timesaving, and low costs. MEFs in 3 × 104 cell/cm2 were fixed by methanol for 5 min and air drying for 5 min. Thereafter, the methanol fixed MEF cells (MT-MEF) were able to be used directly to culture PSCs or stored at room temperature for the future usage. PSCs cultured on MT-MEF could be continuously expanded for over 40 passages with the naïve pluripotency...
May 17, 2018: Scientific Reports
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