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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
#1
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
https://www.readbyqxmd.com/read/28094018/single-cell-analysis-reveals-a-close-relationship-between-differentiating-dopamine-and-subthalamic-nucleus-neuronal-lineages
#2
Nigel Kee, Nikolaos Volakakis, Agnete Kirkeby, Lina Dahl, Helena Storvall, Sara Nolbrant, Laura Lahti, Åsa K Björklund, Linda Gillberg, Eliza Joodmardi, Rickard Sandberg, Malin Parmar, Thomas Perlmann
Stem cell engineering and grafting of mesencephalic dopamine (mesDA) neurons is a promising strategy for brain repair in Parkinson's disease (PD). Refinement of differentiation protocols to optimize this approach will require deeper understanding of mesDA neuron development. Here, we studied this process using transcriptome-wide single-cell RNA sequencing of mouse neural progenitors expressing the mesDA neuron determinant Lmx1a. This approach resolved the differentiation of mesDA and neighboring neuronal lineages and revealed a remarkably close relationship between developing mesDA and subthalamic nucleus (STN) neurons, while also highlighting a distinct transcription factor set that can distinguish between them...
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28094017/predictive-markers-guide-differentiation-to-improve-graft-outcome-in-clinical-translation-of-hesc-based-therapy-for-parkinson-s-disease
#3
Agnete Kirkeby, Sara Nolbrant, Katarina Tiklova, Andreas Heuer, Nigel Kee, Tiago Cardoso, Daniella Rylander Ottosson, Mariah J Lelos, Pedro Rifes, Stephen B Dunnett, Shane Grealish, Thomas Perlmann, Malin Parmar
Stem cell treatments for neurodegenerative diseases are expected to reach clinical trials soon. Most of the approaches currently under development involve transplantation of immature progenitors that subsequently undergo phenotypic and functional maturation in vivo, and predicting the long-term graft outcome already at the progenitor stage remains a challenge. Here, we took an unbiased approach to identify predictive markers expressed in dopamine neuron progenitors that correlate with graft outcome in an animal model of Parkinson's disease through gene expression analysis of >30 batches of grafted human embryonic stem cell (hESC)-derived progenitors...
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28094016/a-single-cell-roadmap-of-lineage-bifurcation-in-human-esc-models-of-embryonic-brain-development
#4
Zizhen Yao, John K Mich, Sherman Ku, Vilas Menon, Anne-Rachel Krostag, Refugio A Martinez, Leon Furchtgott, Heather Mulholland, Susan Bort, Margaret A Fuqua, Ben W Gregor, Rebecca D Hodge, Anu Jayabalu, Ryan C May, Samuel Melton, Angelique M Nelson, N Kiet Ngo, Nadiya V Shapovalova, Soraya I Shehata, Michael W Smith, Leah J Tait, Carol L Thompson, Elliot R Thomsen, Chaoyang Ye, Ian A Glass, Ajamete Kaykas, Shuyuan Yao, John W Phillips, Joshua S Grimley, Boaz P Levi, Yanling Wang, Sharad Ramanathan
During human brain development, multiple signaling pathways generate diverse cell types with varied regional identities. Here, we integrate single-cell RNA sequencing and clonal analyses to reveal lineage trees and molecular signals underlying early forebrain and mid/hindbrain cell differentiation from human embryonic stem cells (hESCs). Clustering single-cell transcriptomic data identified 41 distinct populations of progenitor, neuronal, and non-neural cells across our differentiation time course. Comparisons with primary mouse and human gene expression data demonstrated rostral and caudal progenitor and neuronal identities from early brain development...
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28090751/a-safety-checkpoint-to-eliminate-cancer-risk-of-the-immune-evasive-cells-derived-from-human-embryonic-stem-cells
#5
Jingjin He, Zhili Rong, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) hold great promise in the regenerative therapy of many currently untreatable human diseases. One of the key bottlenecks is the immune rejection of hESC-derived allografts by the recipient. To overcome this challenge, we have established new approaches to induce immune protection of hESC-derived allografts through the co-expression of immune suppressive molecules CTLA4-Ig and PD-L1. However, this in turn raises a safety concern of cancer risk because these hESC-derived cells can evade immune surveillance...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28089995/systematic-evaluation-of-markers-used-for-the-identification-of-human-induced-pluripotent-stem-cells
#6
Sumitha Prameela Bharathan, Kannan Vrindavan Manian, Syed Mohammed Musheer Aalam, Dhavapriya Palani, Prashant Ajit Deshpande, Mankuzhy Damodaran Pratheesh, Alok Srivastava, Shaji Ramachandran Velayudhan
Low efficiency of somatic cell reprogramming and heterogeneity among human induced pluripotent stem cells (hiPSCs) demand extensive characterization of isolated clones before their use in downstream applications. By monitoring human fibroblasts undergoing reprogramming for their morphological changes and expression of fibroblast (CD13), pluripotency markers (SSEA-4 and TRA-1-60) and a retrovirally expressed red fluorescent protein (RV-RFP), we compared the efficiency of these features to identify bona fide hiPSC colonies...
January 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28089909/immunosuppression-via-loss-of-il2r%C3%AE-enhances-long-term-functional-integration-of-hesc-derived-photoreceptors-in-the-mouse-retina
#7
Jie Zhu, Helen Cifuentes, Joseph Reynolds, Deepak A Lamba
Loss of photoreceptors is a common endpoint in degenerative retinal diseases. Human pluripotent stem cells provide a potential source for photoreceptor replacement, but, even in mouse models, the efficiency and efficacy of transplantation-based repair remains poor. In this study, we examined the degree to which immune rejection contributes to these disappointing outcomes using an immunodeficient IL2 receptor γ (IL2rγ)-null mouse model. Our results show that prevention of cell rejection in the normal and degenerating retinal environment significantly improves long-term survival and integration of hESC-derived donor retinal cells...
December 29, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28088685/a-semi-interpenetrating-network-of-polyacrylamide-and-recombinant-basement-membrane-allows-pluripotent-cell-culture-in-a-soft-ligand-rich-microenvironment
#8
Andrew J Price, Eva Y Huang, Vittorio Sebastiano, Alexander R Dunn
The physical properties of the extracellular matrix play an essential role in guiding stem cell differentiation and tissue morphogenesis both in vivo and in vitro. Existing work to investigate the role of matrix mechanics in directing stem cell proliferation, self-renewal, and differentiation has been limited by the poor attachment and survival of human pluripotent cells cultured on soft matrices (Young's modulus E ≲ 1000 Pa). To address this limitation we developed a protocol for generating semi-interpenetrating networks of polyacrylamide and recombinant basement membrane...
December 9, 2016: Biomaterials
https://www.readbyqxmd.com/read/28078490/podocalyxin-as-a-major-pluripotent-marker-and-novel-keratan-sulfate-proteoglycan-in-human-embryonic-and-induced-pluripotent-stem-cells
#9
REVIEW
Hidenao Toyoda, Yuko Nagai, Aya Kojima, Akiko Kinoshita-Toyoda
Podocalyxin (PC) was first identified as a heavily sialylated transmembrane protein of glomerular podocytes. Recent studies suggest that PC is a remarkable glycoconjugate that acts as a universal glyco-carrier. The glycoforms of PC are responsible for multiple functions in normal tissue, human cancer cells, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). PC is employed as a major pluripotent marker of hESCs and hiPSCs. Among the general antibodies for human PC, TRA-1-60 and TRA-1-81 recognize the keratan sulfate (KS)-related structures...
January 11, 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/28069364/compact-mri-for-the-detection-of-teratoma-development-following-intrathecal-human-embryonic-stem-cell-injection-in-nod-scid-mice
#10
Yuval Ramot, Yael S Schiffenbauer, Netanel Amouyal, Nathan Ezov, Michal Steiner, Michal Izrael, Neta Lavon, Arik Hasson, Michel Revel, Abraham Nyska
Stem cells are emerging as a promising new treatment modality for a variety of central nervous system disorders. However, their use is hampered by the potential for the development of teratomas and other tumors. Therefore, there is a crucial need for the development of methods for detecting teratomas in preclinical safety studies. The aim of the current study is to assess the ability of a compact Magnetic Resonance Imaging (MRI) system to detect teratoma formation in mice. Five NOD-SCID mice were injected intrathecally with human embryonic stem cells (hESCs), with two mice serving as controls...
January 6, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28065797/characterising-the-developmental-profile-of-hesc-derived-medium-spiny-neuron-progenitors-and-assessing-mature-neuron-function-using-a-crispr-generated-human-darpp-32-wt-egfp-amp-reporter-line
#11
C P J Hunt, C W Pouton, J M Haynes
In the developing ventral telencephalon, cells of the lateral ganglionic eminence (LGE) give rise to all medium spiny neurons (MSNs). This development occurs in response to a highly orchestrated series of morphogenetic stimuli that pattern the resultant neurons as they develop. Striatal MSNs are characterised by expression of dopamine receptors, dopamine-and cyclic AMP-regulated phosphoprotein (DARPP32) and the neurotransmitter GABA. In this study, we demonstrate that fine tuning WNT and SHH signaling early in human embryonic stem cell differentiation can induce a subpallial progenitor molecular profile...
January 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28052579/poly-trimethylene-carbonate-as-an-elastic-biodegradable-film-for-human-embryonic-stem-cell-derived-retinal-pigment-epithelial-cells
#12
Anni Sorkio, Suvi Haimi, Vincent Verdoold, Kati Juuti-Uusitalo, Dirk Grijpma, Heli Skottman
Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cell therapies show tremendous potential for the treatment of retinal degenerative diseases. A tissue engineering approach, where cells are delivered to the subretinal space on a biodegradable carrier as a sheet, shows great promise for these RPE cell therapies. The aim of the present study was to assess whether a flexible, elastic and biodegradable poly(trimethylene carbonate) (PTMC) film promotes the formation of functional hESC-RPE and performs better than often used biodegradable poly(d,l-lactide) (PDLLA) film...
January 4, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28051155/loss-of-mir-542-3p-enhances-igfbp-1-expression-in-decidualizing-human-endometrial-stromal-cells
#13
Hideno Tochigi, Takeshi Kajihara, Yosuke Mizuno, Yumi Mizuno, Shunsuke Tamaru, Yoshimasa Kamei, Yasushi Okazaki, Jan J Brosens, Osamu Ishihara
Endometrial decidualization represents an essential step for the successful implantation of the embryo; however, the molecular mechanism behind this differentiation process remains unclear. This study aimed to identify novel microRNAs (miRNAs) involved in the regulation of decidual gene expression in human endometrial stromal cells (HESCs). An in vitro analysis of primary undifferentiated and decidualizing HESCs was conducted. HESCs were isolated from hysterectomy specimens from normally cycling premenopausal women with uterine fibroids, who were not on hormonal treatment at the time of surgery...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28042545/comparative-in-vitro-evaluation-of-human-dental-pulp-and-follicle-stem-cell-commitment
#14
Razieh Karamzadeh, Mohamadreza Baghaban Eslaminejad, Ali Sharifi-Zarchi
OBJECTIVE: Pulp and periodontal tissues are well-known sources of mesenchymal stem cells (MSCs) that provide a promising place in tissue engineering and regenerative medicine. The molecular mechanisms underlying commitment and differentiation of dental stem cells that originate from different dental tissues are not fully understood. In this study, we have compared the expression levels of pluripotency factors along with immunological and developmentally-related markers in the culture of human dental pulp stem cells (hDPSCs), human dental follicle stem cells (hDFSCs), and human embryonic stem cells (hESCs)...
2017: Cell Journal
https://www.readbyqxmd.com/read/28042013/antibody-engineering-of-a-cytotoxic-monoclonal-antibody-84-against-human-embryonic-stem-cells-investigating-the-effects-of-multivalency-on-cytotoxicity
#15
Maximilian Klement, Jiyun Zheng, Chengcheng Liu, Heng-Liang Tan, Victor Vai Tak Wong, Andre Boon-Hwa Choo, Dong-Yup Lee, Dave Siak-Wei Ow
Antibody fragments have shown targeted specificity to their antigens, but only modest tissue retention times in vivo and in vitro. Multimerization has been used as a protein engineering tool to increase the number of binding units and thereby enhance the efficacy and retention time of antibody fragments. In this work, we explored the effects of valency using a series of self-assembling polypeptides based on the GCN4 leucine zipper multimerization domain fused to a single-chain variable fragment via an antibody upper hinge sequence...
December 29, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/28038682/comparison-of-a-teratogenic-transcriptome-based-predictive-test-based-on-human-embryonic-versus-inducible-pluripotent-stem-cells
#16
Vaibhav Shinde, Sureshkumar Perumal Srinivasan, Margit Henry, Tamara Rotshteyn, Jürgen Hescheler, Jörg Rahnenführer, Marianna Grinberg, Johannes Meisig, Nils Blüthgen, Tanja Waldmann, Marcel Leist, Jan Georg Hengstler, Agapios Sachinidis
BACKGROUND: Human embryonic stem cells (hESCs) partially recapitulate early embryonic three germ layer development, allowing testing of potential teratogenic hazards. Because use of hESCs is ethically debated, we investigated the potential for human induced pluripotent stem cells (hiPSCs) to replace hESCs in such tests. METHODS: Three cell lines, comprising hiPSCs (foreskin and IMR90) and hESCs (H9) were differentiated for 14 days. Their transcriptome profiles were obtained on day 0 and day 14 and analyzed by comprehensive bioinformatics tools...
December 30, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28026072/activation-of-klf1-enhances-the-differentiation-and-maturation-of-red-blood-cells-from-human-pluripotent-stem-cells
#17
Cheng-Tao Yang, Rui Ma, Richard A Axton, Melany Jackson, A Helen Taylor, Antonella Fidanza, Lamin Marenah, Jan Frayne, Joanne C Mountford, Lesley M Forrester
Blood transfusion is widely used in the clinic but the source of red blood cells (RBCs) is dependent on donors, procedures are susceptible to transfusion-transmitted infections and complications can arise from immunological incompatibility. Clinically-compatible and scalable protocols that allow the production of RBCs from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been described but progress to translation has been hampered by poor maturation and fragility of the resultant cells...
December 27, 2016: Stem Cells
https://www.readbyqxmd.com/read/28010732/the-effect-of-a-germline-mutation-in-the-apc-gene-on-%C3%AE-catenin-in-human-embryonic-stem-cells
#18
Nofar Yedid, Yael Kalma, Mira Malcov, Ami Amit, Revital Kariv, Michal Caspi, Rina Rosin-Arbesfeld, Dalit Ben-Yosef
BACKGROUND: Most cases of colorectal cancer (CRC) are initiated by inactivation mutations in the APC gene, which is a negative regulator of the Wnt-β-catenin pathway. Patients with familial adenomatous polyposis (FAP) inherit a germline mutation in one APC allele, and loss of the second allele leads to the development of polyps that will turn malignant if not removed. It is not fully understood which molecular mechanisms are activated by APC loss and when the loss of the second APC allele occurs...
December 23, 2016: BMC Cancer
https://www.readbyqxmd.com/read/28009074/new-monoclonal-antibodies-to-defined-cell-surface-proteins-on-human-pluripotent-stem-cells
#19
Carmel M O'Brien, Hun S Chy, Qi Zhou, Shiri Blumenfeld, Jack W Lambshead, Xiaodong Liu, Joshua Kie, Bianca D Capaldo, Tung-Liang Chung, Timothy E Adams, Tram Phan, John D Bentley, William J Mckinstry, Karen Oliva, Paul J Mcmurrick, Yu-Chieh Wang, Fernando J Rossello, Geoffrey J Lindeman, Di Chen, Thierry Jarde, Amander T Clark, Helen E Abud, Jane E Visvader, Christian M Nefzger, Jose M Polo, Jeanne F Loring, Andrew L Laslett
The study and application of human pluripotent stem cells (hPSCs) will be enhanced by the availability of well-characterised monoclonal antibodies (mAbs) detecting cell-surface epitopes. Here we report generation of seven new mAbs that detect cell surface proteins present on live and fixed human ES cells (hESCs) and human iPS cells (hiPSCs), confirming our previous prediction that these proteins were present on the cell surface of hPSCs. The mAbs all show a high correlation with POU5F1 (OCT4) expression and other hPSC surface markers (TRA-160 and SSEA-4) in hPSC cultures and detect rare OCT4 positive cells in differentiated cell cultures...
December 23, 2016: Stem Cells
https://www.readbyqxmd.com/read/28003831/in-vitro-osteogenic-potential-of-green-fluorescent-protein-labelled-human-embryonic-stem-cell-derived-osteoprogenitors
#20
Intekhab Islam, Gopu Sriram, Mingming Li, Yu Zou, Lulu Li, Harish K Handral, Vinicus Rosa, Tong Cao
Cellular therapy using stem cells in bone regeneration has gained increasing interest. Various studies suggest the clinical utility of osteoprogenitors-like mesenchymal stem cells in bone regeneration. However, limited availability of mesenchymal stem cells and conflicting evidence on their therapeutic efficacy limit their clinical application. Human embryonic stem cells (hESCs) are potentially an unlimited source of healthy and functional osteoprogenitors (OPs) that could be utilized for bone regenerative applications...
2016: Stem Cells International
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