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https://www.readbyqxmd.com/read/28205557/experimental-study-of-the-biological-properties-of-human-embryonic-stem-cell-derived-retinal-progenitor-cells
#1
Jingzhi Shao, Peng-Yi Zhou, Guang-Hua Peng
Retinal degenerative diseases are among the leading causes of blindness worldwide, and cell replacement is considered as a promising therapeutic. However, the resources of seed cells are scarce. To further explore this type of therapy, we adopted a culture system that could harvest a substantial quantity of retinal progenitor cells (RPCs) from human embryonic stem cells (hESCs) within a relatively short period of time. Furthermore, we transplanted these RPCs into the subretinal spaces of Royal College of Surgeons (RCS) rats...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199886/construction-of-tissue-engineered-full-thickness-cornea-substitute-using-limbal-epithelial-cell-like-and-corneal-endothelial-cell-like-cells-derived-from-human-embryonic-stem-cells
#2
Canwei Zhang, Liqun Du, Peng Sun, Lin Shen, Jing Zhu, Kunpeng Pang, Xinyi Wu
The aim of this study was to construct a full-thickness artificial cornea substitute in vitro by coculturing limbal epithelial cell-like (LEC-like) cells and corneal endothelial cell-like (CEC-like) cells derived from human embryonic stem cells (hESCs) on APCM scaffold. A 400 μm thickness, 11 mm diameter APCM lamella containing Bowman's membrane was prepared as the scaffold using trephine and a special apparatus made by ourselves. LEC-like cells and CEC-like cells, derived from hESCs as our previously described, were cocultured on the scaffold using a special insert of 24-well plates that enabled seeding both sides of the scaffold...
February 6, 2017: Biomaterials
https://www.readbyqxmd.com/read/28186679/directed-differentiation-of-human-embryonic-stem-cells-toward-placode-derived-spiral-ganglion-like-sensory-neurons
#3
Akihiro J Matsuoka, Zachery D Morrissey, Chaoying Zhang, Kazuaki Homma, Abdelhak Belmadani, Charles A Miller, Duncan M Chadly, Shun Kobayashi, Alexandra N Edelbrock, Miho Tanaka-Matakatsu, Donna S Whitlon, Ljuba Lyass, Tammy L McGuire, Samuel I Stupp, John A Kessler
The ability to generate spiral ganglion neurons (SGNs) from stem cells is a necessary prerequisite for development of cell-replacement therapies for sensorineural hearing loss. We present a protocol that directs human embryonic stem cells (hESCs) toward a purified population of otic neuronal progenitors (ONPs) and SGN-like cells. Between 82% and 95% of these cells express SGN molecular markers, they preferentially extend neurites to the cochlear nucleus rather than nonauditory nuclei, and they generate action potentials...
December 10, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28185769/intact-wound-repair-activity-of-human-mesenchymal-stem-cells-after-ym155-mediated-selective-ablation-of-undifferentiated-human-embryonic-stem-cells
#4
Keun-Tae Kim, Ho-Chang Jeong, C-Yoon Kim, Eun-Young Kim, Si-Hyun Heo, Seung-Ju Cho, Ki-Sung Hong, Hyuk-Jin Cha
BACKGROUND: Risk of teratoma formation during human pluripotent stem cell (hPSC)-based cell therapy is one of the technical hurdles that must be resolved before their wider clinical application. To this end, selective ablation of undifferentiated hPSCs has been achieved using small molecules whose application should be safe for differentiated cells derived from the hPSCs. OBJECTIVE: However, the functional safety of such small molecules in the cells differentiated from hPSCs has not yet been extensively validated...
January 31, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28182681/a-standardized-human-embryoid-body-platform-for-the-detection-and-analysis-of-teratogens
#5
Anthony Flamier, Supriya Singh, Theodore P Rasmussen
Teratogens are compounds that can induce birth defects upon exposure of the developing fetus. To date, most teratogen studies utilize pregnant rodents to determine compound teratogenicity in vivo. However, this is a low throughput approach that cannot easily meet the need for comprehensive high-volume teratogen assessment, a goal of the US Environmental Protection Agency. In addition, rodent and human development differ substantially, and therefore the use of assays using relevant human cells has utility. For these reasons, interest has recently focused on the use of human embryonic stem cells for teratogen assessment...
2017: PloS One
https://www.readbyqxmd.com/read/28182296/ways-out-of-the-patenting-prohibition-human-parthenogenetic-and-induced-pluripotent-stem-cells
#6
Hannah Schickl, Matthias Braun, Peter Dabrock
According to the judgement of the European Court of Justice in 2014, human parthenogenetic stem cells are excluded from the patenting prohibition of procedures based on hESC by the European Biopatent Directive, because human parthenotes are not human embryos. This article is based on the thesis that in light of the technological advances in the field of stem cell research, the attribution of the term 'human embryo' to certain entities on a descriptive level as well as the attribution of a normative protection status to certain entities based on the criterion of totipotency, are becoming increasingly unclear...
February 9, 2017: Bioethics
https://www.readbyqxmd.com/read/28170184/regeneration-of-articular-cartilage-by-human-esc-derived-mesenchymal-progenitors-treated-sequentially-with-bmp-2-and-wnt5a
#7
Jason D Gibson, Michael B O'Sullivan, Farhang Alaee, David N Paglia, Ryu Yoshida, Rosa M Guzzo, Hicham Drissi
The success of cell-based therapies to restore joint cartilage requires an optimal source of reparative progenitor cells and tight control of their differentiation into a permanent cartilage phenotype. Bone morphogenetic protein 2 (BMP-2) has been extensively shown to promote mesenchymal cell differentiation into chondrocytes in vitro and in vivo. Conversely, developmental studies have demonstrated decreased chondrocyte maturation by Wingless-Type MMTV Integration Site Family, Member 5A (Wnt5a). Thus, we hypothesized that treatment of human embryonic stem cell (hESC)-derived chondroprogenitors with BMP-2 followed by Wnt5a may control the maturational progression of these cells into a hyaline-like chondrocyte phenotype...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28169114/coculturing-with-endothelial-cells-promotes-in-vitro-maturation-and-electrical-coupling-of-human-embryonic-stem-cell-derived-cardiomyocytes
#8
Jennifer Pasquier, Renuka Gupta, Damien Rioult, Jessica Hoarau-Véchot, Raphael Courjaret, Khaled Machaca, Jassim Al Suwaidi, Edouard G Stanley, Shahin Rafii, David A Elliott, Charbel Abi Khalil, Arash Rafii
BACKGROUND: Pluripotent human embryonic stem cells (hESC) are a promising source of repopulating cardiomyocytes. We hypothesized that we could improve maturation of cardiomyocytes and facilitate electrical interconnections by creating a model that more closely resembles heart tissue; that is, containing both endothelial cells (ECs) and cardiomyocytes. METHODS: We induced cardiomyocyte differentiation in the coculture of an hESC line expressing the cardiac reporter NKX2...
January 10, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28167527/characterization-of-h-type-1-and-type-1-n-acetyllactosamine-glycan-epitopes-on-ovarian-cancer-specifically-recognized-by-the-anti-glycan-monoclonal-antibody-mab-a4
#9
Matthew Choo, Heng Liang Tan, Vanessa Ding, Roberto Castangia, Omar Belgacem, Brian Liau, Lauren Hartley-Tassell, Stuart M Haslam, Anne Dell, Andre Choo
Cancer-specific glycans of ovarian cancer are promising epitopes for targeting with monoclonal antibodies (mAb). Despite their potential, structural characterization of these glycan epitopes remains a significant challenge in mAb preclinical development. Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 out of 19 ovarian cancer (OC) and 8 out of 14 breast cancer cell lines tested. Normal cell lines and tissue were unstained by mAb-A4...
February 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28161299/cell-culture-chamber-with-gas-supply-for-prolonged-recording-of-human-neuronal-cells-on-microelectrode-array
#10
Joose Kreutzer, Laura Ylä-Outinen, Antti-Juhana Mäki, Mervi Ristola, Susanna Narkilahti, Pasi Kallio
BACKGROUND: Typically, live cell analyses are performed outside an incubator in an ambient air, where the lack of sufficient CO2 supply results in a fast change of pH and the high evaporation causes concentration drifts in the culture medium. That limits the experiment time for tens of minutes. In many applications, e.g. in neurotoxicity studies, a prolonged measurement of extracellular activity is, however, essential. NEW METHOD: We demonstrate a simple cell culture chamber that enables stable culture conditions during prolonged extracellular recordings on a microelectrode array (MEA) outside an incubator...
February 1, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28157212/wnt-%C3%AE-catenin-signaling-pathway-regulates-non-tumorigenesis-of-human-embryonic-stem-cells-co-cultured-with-human-umbilical-cord-mesenchymal-stem-cells
#11
Yu-Hsun Chang, Tang-Yuan Chu, Dah-Ching Ding
Human pluripotent stem cells harbor hope in regenerative medicine, but have limited application in treating clinical diseases due to teratoma formation. Our previous study has indicated that human umbilical cord mesenchymal stem cells (HUCMSC) can be adopted as non-teratogenenic feeders for human embryonic stem cells (hESC). This work describes the mechanism of non-tumorigenesis of that feeder system. In contrast with the mouse embryonic fibroblast (MEF) feeder, HUCMSC down-regulates the WNT/β-catenin/c-myc signaling in hESC...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28157205/epex-epcam-and-oct4-or-klf4-alone-are-sufficient-to-generate-induced-pluripotent-stem-cells-through-stat3-and-hif2%C3%AE
#12
I-I Kuan, Kang-Hao Liang, Yi-Ping Wang, Ting-Wen Kuo, Yaa-Jyuhn James Meir, Sareina Chiung-Yuan Wu, Shang-Chih Yang, Jean Lu, Han-Chung Wu
Epithelial cell adhesion molecule (EpCAM) was reported to be cleaved into extracellular domain of EpCAM (EpEX) and intracellular domain of EpCAM (EpICD). We previously reported that EpCAM serves as a potent stem cell marker which is highly and selectively expressed by undifferentiated rather than differentiated hESC. However, the functional role of EpCAM remains elusive. Here, we found that EpEX and EpCAM enhance the efficiency of OSKM reprogramming. Interestingly, Oct4 or Klf4 alone, but not Sox2, can successfully reprogram fibroblasts into iPSCs with EpEX and EpCAM...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28153093/human-amniocytes-are-receptive-to-chemically-induced-reprogramming-to-pluripotency
#13
Kate E Hawkins, Dafni Moschidou, Danilo Faccenda, Wasco Wruck, Alex Martin-Trujillo, Kwan-Leong Hau, Anna Maria Ranzoni, Veronica Sanchez-Freire, Fabio Tommasini, Simon Eaton, Paolo De Coppi, David Monk, Michelangelo Campanella, Adrian J Thrasher, James Adjaye, Pascale V Guillot
Restoring pluripotency using chemical compounds alone would be a major step forward in developing clinical-grade pluripotent stem cells, but this has not yet been reported in human cells. We previously demonstrated that VPA_AFS cells, human amniocytes cultivated with valproic acid (VPA) acquired functional pluripotency while remaining distinct from human embryonic stem cells (hESCs), questioning the relationship between the modulation of cell fate and molecular regulation of the pluripotency network. Here, we used single-cell analysis and functional assays to reveal that VPA treatment resulted in a homogeneous population of self-renewing non-transformed cells that fulfill the hallmarks of pluripotency, i...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28139119/proteomic-analysis-of-human-pluripotent-stem-cell-cardiomyogenesis-revealed-altered-expression-of-metabolic-enzymes-and-pdlim5-isoforms
#14
Sarah Anna Konze, Sebastian Werneburg, Astrid Oberbeck, Ruth Olmer, Henning Kempf, Monica Jara-Avaca, Andreas Pich, Robert Zweigerdt, Falk Fritz Reinhold Buettner
Human pluripotent stem cells (hPSCs), both embryonic (hESCs) and induced (hiPSCs), can be differentiated into derivatives of the three germ layers and are promising tools in regenerative medicine. Cardiovascular diseases are the top-ranking cause of premature death worldwide and cell replacement therapies based on in vitro differentiated cardiomyocytes might provide a promising perspective to cure patients in the future. The molecular processes during hPSC cardiomyogenesis are far from being fully understood and we thus have focused here on characterizing the proteome along hESC in vitro differentiation into cardiomyocytes (CMs)...
January 31, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28132887/pc1-3-deficiency-impacts-pro-opiomelanocortin-processing-in-human-embryonic-stem-cell-derived-hypothalamic-neurons
#15
Liheng Wang, Lina Sui, Sunil K Panigrahi, Kana Meece, Yurong Xin, Jinrang Kim, Jesper Gromada, Claudia A Doege, Sharon L Wardlaw, Dieter Egli, Rudolph L Leibel
We recently developed a technique for generating hypothalamic neurons from human pluripotent stem cells. Here, as proof of principle, we examine the use of these cells in modeling of a monogenic form of severe obesity: PCSK1 deficiency. The cognate enzyme, PC1/3, processes many prohormones in neuroendocrine and other tissues. We generated PCSK1 (PC1/3)-deficient human embryonic stem cell (hESC) lines using both short hairpin RNA and CRISPR-Cas9, and investigated pro-opiomelanocortin (POMC) processing using hESC-differentiated hypothalamic neurons...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28131957/the-role-of-methylation-dna-polymorphisms-and-micrornas-on-hla-g-expression-in-human-embryonic-stem-cells
#16
A Verloes, C Spits, M Vercammen, M Geens, J LeMaoult, K Sermon, W Coucke, H Van de Velde
The human leukocyte antigen (HLA)-G gene seems to play a pivotal role in maternal tolerance to the fetus. Little is known about HLA-G expression and its molecular control during in vivo human embryogenesis. Human embryonic stem cells (hESC) provide an interesting in vitro model to study early human development. Different studies reported discrepant findings on whether HLA-G mRNA and protein are present or absent in hESC. Several lines of evidence indicate that promoter CpG methylation and 3' untranslated region (3'UTR) polymorphisms may influence HLA-G expression...
January 9, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28116670/an-inducible-crispr-on-system-for-controllable-gene-activation-in-human-pluripotent-stem-cells
#17
Jianying Guo, Dacheng Ma, Rujin Huang, Jia Ming, Min Ye, Kehkooi Kee, Zhen Xie, Jie Na
Human pluripotent stem cells (hPSCs) are an important system to study early human development, model human diseases, and develop cell replacement therapies. However, genetic manipulation of hPSCs is challenging and a method to simultaneously activate multiple genomic sites in a controllable manner is sorely needed. Here, we constructed a CRISPR-ON system to efficiently upregulate endogenous genes in hPSCs. A doxycycline (Dox) inducible dCas9-VP64-p65-Rta (dCas9-VPR) transcription activator and a reverse Tet transactivator (rtTA) expression cassette were knocked into the two alleles of the AAVS1 locus to generate an iVPR hESC line...
January 23, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28110217/induced-dopaminergic-neurons-a-new-promise-for-parkinson-s-disease
#18
Zhimin Xu, Xingkun Chu, Houbo Jiang, Haley Schilling, Shengdi Chen, Jian Feng
Motor symptoms that define Parkinson's disease (PD) are caused by the selective loss of nigral dopaminergic (DA) neurons. Cell replacement therapy for PD has been focused on midbrain DA neurons derived from human fetal mesencephalic tissue, human embryonic stem cells (hESC) or human induced pluripotent stem cells (iPSC). Recent development in the direct conversion of human fibroblasts to induced dopaminergic (iDA) neurons offers new opportunities for transplantation study and disease modeling in PD. The iDA neurons are generated directly from human fibroblasts in a short period of time, bypassing lengthy differentiation process from human pluripotent stem cells and the concern for potentially tumorigenic mitotic cells...
January 16, 2017: Redox Biology
https://www.readbyqxmd.com/read/28106884/excess-reactive-oxygen-species-production-mediates-monoclonal-antibody-induced-human-embryonic-stem-cell-death-via-oncosis
#19
Ji Yun Zheng, Heng Liang Tan, Paul Thomas Matsudaira, Andre Choo
Antibody-mediated cell killing has significantly facilitated the elimination of undesired cells in therapeutic applications. Besides the well-known Fc-dependent mechanisms, pathways of antibody-induced apoptosis were also extensively studied. However, with fewer studies reporting the ability of antibodies to evoke an alternative form of programmed cell death, oncosis, the molecular mechanism of antibody-mediated oncosis remains underinvestigated. In this study, a monoclonal antibody (mAb), TAG-A1 (A1), was generated to selectively kill residual undifferentiated human embryonic stem cells (hESC) so as to prevent teratoma formation upon transplantation of hESC-derived products...
January 20, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28098961/angiogenic-and-osteogenic-regeneration-in-rats-via-calcium-phosphate-scaffold-and-endothelial-cell-coculture-with-hbmscs-hucmscs-hipsc-mscs-and-hesc-mscs
#20
Wenchuan Chen, Xian Liu, Qianmin Chen, Chongyun Bao, Liang Zhao, Zhimin Zhu, Hockin H K Xu
Angiogenesis is a limiting factor in regenerating large bone defects. The objective of this study was to investigate angiogenic and osteogenic effects of coculture on calcium phosphate cement (CPC) scaffold using human umbilical vein endothelial cells (hUVECs) and mesenchymal stem cells (MSCs) from different origins for the first time. hUVECs were cocultured with four types of cells: human umbilical cord MSCs (hUCMSCs), human bone marrow MSCs (hBMSCs), and MSCs from induced pluripotent stem cells (hiPSC-MSCs) and embryonic stem cells (hESC-MSCs)...
January 18, 2017: Journal of Tissue Engineering and Regenerative Medicine
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