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https://www.readbyqxmd.com/read/28645575/prediction-of-drug-induced-immune-mediated-hepatotoxicity-using-hepatocyte-like-cells-derived-from-human-embryonic-stem-cells
#1
Dong Eon Kim, Mi-Jin Jang, Young Ran Kim, Joo-Young Lee, Eun Byul Cho, Eunha Kim, Yeji Kim, Mi Young Kim, Won-Il Jeong, Seyun Kim, Yong-Mahn Han, Seung-Hyo Lee
Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28645561/boris-up-regulates-oct4-via-histone-methylation-to-promote-cancer-stem-cell-like-properties-in-human-liver-cancer-cells
#2
Qiuying Liu, Kefei Chen, Zhongjian Liu, Yuan Huang, Rongce Zhao, Ling Wei, Xiaoqin Yu, Jingyang He, Jun Liu, Jianguo Qi, Yang Qin, Bo Li
Accumulating evidence has revealed the importance of cancer stem cells (CSCs) in chemoresistance and recurrence. BORIS, a testes-specific CTCF paralog, has been shown to be associated with stemness traits of embryonic cancer cells and epithelial CSCs. We previously reported that BORIS is correlated with the expression of the CSC marker CD90 in hepatocellular carcinoma (HCC). These results encourage us to wonder whether BORIS exerts functions on CSC-like traits of human liver cancer cells. Here, we report that BORIS was enriched in HCC tissues...
June 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28643455/pathways-governing-development-of-stem-cell-derived-pancreatic-%C3%AE-cells-lessons-from-embryogenesis
#3
Sara Al-Khawaga, Bushra Memon, Alexandra E Butler, Shahrad Taheri, Abdul B Abou-Samra, Essam M Abdelalim
The loss of functional β cells leads to development of diabetes. Several studies have shown that β cells are specified through several stages of progenitors during pancreas development, each stage defined by the expression of specific transcription factors (TFs). Understanding signalling pathways that control the differentiation and specification processes during embryogenesis will facilitate efforts to obtain functional β cells in vitro. Our current knowledge of the mechanisms involved in pancreatic β cell development and survival under normal or diabetic conditions has come largely from animal studies...
June 22, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28643250/genome-editing-in-mouse-zygotes-and-embryonic-stem-cells-by-introducing-sgrna-cas9-expressing-plasmids
#4
Taichi Noda, Asami Oji, Masahito Ikawa
In mammalian cells, genome editing with the single guide RNA (sgRNA)/Cas9 complex allows for high targeting efficiency within a relatively short time frame with the added benefits of being low cost and easy to design. sgRNA/Cas9-mediated editing in mouse zygotes has accelerated the analysis of gene functions and the generation of mouse models of human diseases. Despite the benefits, this method still suffers from several problems, such as mosaicism in the founder generation which complicates genotyping and phenotypical analyses, and the low efficiency of more complicated genome editing...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28642734/the-short-stature-homeobox-containing-gene-shox-shox-is-required-for-the-regulation-of-cell-proliferation-and-bone-differentiation-in-zebrafish-embryo-and-human-mesenchymal-stem-cells
#5
Tomoaki Yokokura, Hiroyasu Kamei, Takashi Shibano, Daisuke Yamanaka, Rie Sawada-Yamaguchi, Fumihiko Hakuno, Shin-Ichiro Takahashi, Toshiaki Shimizu
The short-stature homeobox-containing gene (SHOX) was originally discovered as one of genes responsible for idiopathic short-stature syndromes in humans. Previous studies in animal models have shown the evolutionarily conserved link between this gene and skeletal formation in early embryogenesis. Here, we characterized developmental roles of shox/SHOX in zebrafish embryos and human mesenchymal stem cells (hMSCs) using loss-of-function approaches. Morpholino oligo-mediated knockdown of zebrafish shox markedly hindered cell proliferation in the anterior region of the pharyngula embryos, which was accompanied by reduction in the dlx2 expression at mesenchymal core sites for future pharyngeal bones...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28641611/-dmso-promotes-hematopoietic-differentiation-of-human-embryonic-stem-cells-in-vitro
#6
Hong-Tao Wang, Meng-Ge Wang, Xin Liu, Pei Su, Lei-Sheng Zhang, Cui-Cui Liu, Yu Wang, Dan Wu, Qian Tu, Jia-Xi Zhou
OBJECTIVE: To explore the role of dimethyl sulfoxide (DMSO) in the hematopoietic differentiation of human embryonic stem cells (hESCs). METHODS: The role of DMSO in hematopoietic differentiation of hESC was investigated by using a established stepwise hematopoietic differentiation system from hESC, immunofluorescouse assay and flow cytometry. Furthermore, the window phase of DMSO action was explored by adding it to the different stage of hematopoietic differentiation...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641519/neural-stem-cells-and-human-induced-pluripotent-stem-cells-to-model-rare-cns-diseases
#7
Lidia De Filippis, Cristina Zalfa, Daniela Ferrari
Despite the great effort spent over the last decades to unravel the pathological mechanisms underpinning the development of central nervous system disorders, most of them remain still unclear. In particular, the study of rare brain diseases is hurdled by the lack of post-mortem samples and of reliable epidemiological studies, thus the setting of in vitro modeling systems appears essential to dissect the puzzle of genetic and environmental alterations affecting neural cells viability and functionality The isolation and expansion in vitro of embryonic (ESC) and fetal neural stem cells (NSC) from human tissue has efficiently allowed to model several neurological diseases "in a dish" and has also provided a novel platform to test potential therapeutic strategies in a pre-clinical setting...
June 15, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28637969/development-of-a-patient-derived-induced-pluripotent-stem-cell-model-for-the-investigation-of-scn5a-d1275n-related-cardiac-sodium-channelopathy
#8
Mamoru Hayano, Takeru Makiyama, Tsukasa Kamakura, Hiroshi Watanabe, Kenichi Sasaki, Shunsuke Funakoshi, Yimin Wuriyanghai, Suguru Nishiuchi, Takeshi Harita, Yuta Yamamoto, Hirohiko Kohjitani, Sayako Hirose, Fumika Yokoi, Jiarong Chen, Osamu Baba, Takahiro Horie, Kazuhisa Chonabayashi, Seiko Ohno, Futoshi Toyoda, Yoshinori Yoshida, Koh Ono, Minoru Horie, Takeshi Kimura
BACKGROUND: TheSCN5Agene encodes the α subunit of the cardiac voltage-gated sodium channel, NaV1.5. The missense mutation, D1275N, has been associated with a range of unusual phenotypes associated with reduced NaV1.5 function, including cardiac conduction disease and dilated cardiomyopathy. Curiously, the reported biophysical properties ofSCN5A-D1275N channels vary with experimental system.Methods and Results:First, using a human embryonic kidney (HEK) 293 cell-based heterologous expression system, theSCN5A-D1275N channels showed similar maximum sodium conductance but a significantly depolarizing shift of activation gate (+10 mV) compared to wild type...
June 20, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28637827/islet-encapsulation-physiological-possibilities-and-limitations
#9
Olle Korsgren
A logical cure for type 1 diabetes (T1D) involves replacing the lost insulin-producing cells with new ones, preferably cells from a well-characterized and unlimited source of human insulin-producing cells. This straightforward and simple solution to provide a cure for T1D is immensely attractive but entails at least two inherent and thus far unresolved hurdles: 1) provision of an unlimited source of functional human insulin-producing cells and 2) prevention of rejection without the side effects of systemic immunosuppression...
July 2017: Diabetes
https://www.readbyqxmd.com/read/28637759/role-of-jnk-pathway-in-varicella-zoster-virus-lytic-infection-and-reactivation
#10
Sravya Kurapati, Tomohiko Sadaoka, Labchan Rajbhandari, Balaji Jagdish, Priya Shukla, Yong Jun Kim, Gabsang Lee, Jeffrey I Cohen, Arun Venkatesan
Mechanisms of neuronal infection by varicella-zoster virus (VZV) have been challenging to study due to the relatively strict human tropism of the virus and the paucity of tractable experimental models. Cellular mitogen activated protein kinases (MAPKs) have been shown to play a role in VZV infection of non-neuronal cells, with distinct consequences on infectivity in differing cell types. Here, we utilize several human neuronal culture systems to investigate the role of one such MAPK, the c-Jun N-terminal kinase (JNK), in VZV lytic infection and reactivation...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28636235/stem-cell-based-tooth-and-periodontal-regeneration
#11
Lei Hu, Yi Liu, Songlin Wang
Currently regeneration of tooth and periodontal damage still remains great challenge. Stem cell-based tissue engineering raised novel therapeutic strategies for tooth and periodontal repair. Stem cells for tooth and periodontal regeneration include dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), stem cells from the dental apical papilla (SCAPs), and stem cells from human exfoliated deciduous teeth (SHEDs), dental follicle stem cells (DFSCs), dental epithelial stem cells (DESCs), bone marrow mesenchymal stem cells (BMMSCs), adipose-derived stem cells (ADSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)...
June 21, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28636206/retinal-vascular-injuries-and-intravitreal-human-embryonic-stem-cell-derived-haemangioblasts
#12
Jin-Da Wang, Ying An, Jing-Shang Zhang, Xiu-Hua Wan, Wei Zhang, Robert Lanza, Shi-Jiang Lu, Jost B Jonas, Liang Xu
OBJECTIVE: To investigate whether intravitreally applied haemangioblasts (HB) derived from human embryonic stem cells (hESCs) are helpful for the repair of vascular damage caused in animals by an oxygen-induced retinopathy (OIR), by an induced diabetic retinopathy (DR) or by an induced retinal ischaemia with subsequent reperfusion. METHODS: Human embryonic stem cell-derived HBs were transplanted intravitreally into C57BL/6J mice (OIR model), into male Wistar rats with an induced DR and into male Wistar rats undergoing induced retinal ischaemia with subsequent reperfusion...
June 21, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28633916/novel-variant-of-oct4b4-is-differentially-expressed-in-human-embryonic-stem-and-embryonic-carcinoma-cells
#13
Ensieh M Poursani, Majid Mehravar, Bahram Mohammad Soltani, Seyed Javad Mowla
POU domain proteins are an important family of transcription factors that regulates cell type-specific gene expression. One of the most crucial members of this family that maintains pluripotency and self-renewal of embryonic stem cells is POU5F1/OCT4. The OCT4 gene can generate several variants under different situations/cell types includes OCT4A that is the major factor sustains pluripotency in embryonic stem and embryonic carcinoma cells, and also OCT4B and OCT4B1, which might be transcribed from a different potential promoter located in intron1 and are expressed in various tissues and cell types...
June 17, 2017: Gene
https://www.readbyqxmd.com/read/28633106/selective-photocytotoxicity-of-anthrols-on-cancer-stem-like-cells-the-effect-of-quinone-methides-or-reactive-oxygen-species
#14
Lidija Uzelac, Đani Škalamera, Kata Mlinarić-Majerski, Nikola Basarić, Marijeta Kralj
Cancer stem cells (CSCs) are a subpopulation of cancer cells that share properties of embryonic stem cells like pluripotency and self-renewal and show increased resistance to chemo- and radiotherapy. Targeting CSC, rather than cancer cells in general, is a novel and promising strategy for cancer treatment. Novel therapeutic approaches, such as photodynamic therapy (PDT) have been investigated. A promising group of phototherapeutic agents are reactive intermediates - quinone methides (QMs). This study describes preparation of QM precursor, 2-hydroxy-3-hydroxymethylanthracene (2) and a detailed photochemical and photobiological investigation on similar anthracene derivatives 3 and 4...
June 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28633015/haploidy-in-humans-an-evolutionary-and-developmental-perspective
#15
REVIEW
Ido Sagi, Nissim Benvenisty
Although haploidy has not been observed in vertebrates, its natural occurrence in various eukaryotic species that had diverged from diploid ancestors suggests that there is an innate capacity for an organism to regain haploidy and that haploidy may confer evolutionary benefits. Haploid embryonic stem cells have been experimentally generated from mouse, rat, monkey, and humans. Haploidy results in major differences in cell size and gene expression levels while also affecting parental imprinting, X chromosome inactivation, and mitochondrial metabolism genes...
June 19, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28628110/colonic-organoids-derived-from-human-induced-pluripotent-stem-cells-for-modeling-colorectal-cancer-and-drug-testing
#16
Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans, Shuibing Chen
With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. We applied this strategy to iPSCs derived from patients with familial adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and we generated COs that exhibit enhanced WNT activity and increased epithelial cell proliferation, which we used as a platform for drug testing...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28627682/microvesicles-released-from-human-embryonic-stem-cell-derived-mesenchymal-stem-cells-inhibit-proliferation-of-leukemia-cells
#17
Yuan Ji, Yongbin Ma, Xiang Chen, Xianyan Ji, Jianyi Gao, Lei Zhang, Kai Ye, Fuhao Qiao, Yao Dai, Hui Wang, Xiangmei Wen, Jiang Lin, Jiabo Hu
Human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSCs) are able to inhibit proliferation of leukemia cells. Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSC‑MVs) might play an important part in antitumor activity. Microvesicles were isolated by ultracentrifugation and identified under a scanning electron microscopy and transmission electron microscope separately. After 48-h cocultured with hESC‑MSCs and hESC‑MSC‑MVs, the number of K562 and HL60 was counted and tumor cell viability was measured by CCK8 assay...
June 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28626601/long-term-efficacy-of-gmp-grade-xeno-free-hesc-derived-rpe-cells-following-transplantation
#18
Trevor J McGill, Osnat Bohana-Kashtan, Jonathan W Stoddard, Michael D Andrews, Neelay Pandit, Lior R Rosenberg-Belmaker, Ofer Wiser, Limor Matzrafi, Eyal Banin, Benjamin Reubinoff, Nir Netzer, Charles Irving
PURPOSE: Retinal pigment epithelium (RPE) dysfunction underlies the retinal degenerative process in age-related macular degeneration (AMD), and thus RPE cell replacement provides an optimal treatment target. We characterized longitudinally the efficacy of RPE cells derived under xeno-free conditions from clinical and xeno-free grade human embryonic stem cells (OpRegen) following transplantation into the subretinal space of Royal College of Surgeons (RCS) rats. METHODS: Postnatal (P) day 20 to 25 RCS rats (n = 242) received a single subretinal injection of 25,000 (low)-, 100,000 (mid)-, or 200,000 (high)-dose xeno-free RPE cells...
June 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28626459/the-immunogenicity-and-immune-tolerance-of-pluripotent-stem-cell-derivatives
#19
REVIEW
Xin Liu, Wenjuan Li, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into all cell types in human body, and therefore hold great potential for cell therapy of currently incurable diseases including neural degenerative diseases, heart failure, and macular degeneration. This potential is further underscored by the promising safety and efficacy data from the ongoing clinical trials of hESC-based therapy of macular degeneration. However, one main challenge for the clinical application of hESC-based therapy is the allogeneic immune rejection of hESC-derived cells by the recipient...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28626363/hoxb4-increases-runx1-expression-to-promote-the-de-novo-formation-of-multipotent-hematopoietic-cells
#20
Nadine Teichweyde, Peter A Horn, Hannes Klump
BACKGROUND: The de novo generation of patient-specific hematopoietic stem and progenitor cells from induced pluripotent stem cells (iPSCs) has become a promising approach for cell replacement therapies in the future. However, efficient differentiation protocols for producing fully functional human hematopoietic stem cells are still missing. In the mouse model, ectopic expression of the human homeotic selector protein HOXB4 has been shown to enforce the development of hematopoietic stem cells (HSCs) in differentiating pluripotent stem cell cultures...
June 2017: Transfusion Medicine and Hemotherapy
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