0060] The term cell proliferation control means a procedure in which cell proliferative capacity is stopped at a desired time, the cell concentration is maintained without significant damage affecting the viability of cells to the cells, and subsequently cell proliferation is restarted at a desired time. In other words, in a method for controlling cell proliferation of the present invention, the proliferation of primate pluripotent stem cells can be inhibited with a maintenance medium for pluripotent stem cells of the present invention, and after a desired period elapsed, the proliferation of primate pluripotent stem cells can be promoted with a culture medium containing glucose. In a method for controlling cell proliferation of the present invention, the growth rate and the morphology of pluripotent stem cells following the procedure in which the proliferation is inhibited with a maintenance medium for pluripotent stem cells of the present invention, and after an inhibition period passed, the ...
Induced pluripotent stem cell technology makes in vitro reprogramming of somatic cells from individuals with various genetic backgrounds possible. By applying this technology, it is possible to produce pluripotent stem cells from biopsy samples of arbitrarily selected individuals with various genetic backgrounds and to subsequently maintain, expand, and stock these cells. From these induced pluripotent stem cells, target cells and tissues can be generated after certain differentiation processes. These target cells/tissues are expected to be useful in regenerative medicine, disease modeling, drug screening, toxicology testing, and proof-of-concept studies in drug development. Therefore, the number of publications concerning induced pluripotent stem cells has recently been increasing rapidly, demonstrating that this technology has begun to infiltrate many aspects of stem cell biology and medical applications. In this review, we discuss the perspectives of induced pluripotent stem cell technology ...
SAN DIEGO, December 15, 2017 - ViaCyte, Inc., a privately-held regenerative medicine company, today announced that the California Institute for Regenerative Medicine (CIRM) approved a grant of $1.4 million to support the initial development of immune-evasive pluripotent stem cell lines. The focus of the project will be to genetically engineer the Companys CyT49 pluripotent stem cell line. ViaCytes proprietary CyT49 cell line is well characterized and has been used to manufacture cell replacement product candidates that have been reviewed and allowed for use in clinical trials by multiple regulatory authorities.. One of the main challenges in developing an off-the-shelf cell therapy is the potential for immune rejection of implanted cells. Genetic engineering of a pluripotent stem cell line may make it possible to generate cell therapies from a single source that will not be rejected by the immune system. For diabetes, pluripotent stem cells have the potential of providing an unlimited supply ...
The potential for directed differentiation of human-induced pluripotent stem (iPS) cells to functional postmitotic neuronal phenotypes is unknown. Following methods shown to be effective at generating motor neurons from human embryonic stem cells (hESCs), we found that once specified to a neural lineage, human iPS cells could be differentiated to form motor neurons with a similar efficiency as hESCs. Human iPS-derived cells appeared to follow a normal developmental progression associated with motor neuron formation and possessed prototypical electrophysiological properties. This is the first demonstration that human iPS-derived cells are able to generate electrically active motor neurons. These findings demonstrate the feasibility of using iPS-derived motor neuron progenitors and motor neurons in regenerative medicine applications and in vitro modeling of motor neuron diseases ...
Since it was first demonstrated that induced pluripotent stem cells (iPS cells) could be derived from mature cells, significant progress has been made in the field of acquisition, characteristics, identification and application of iPS cells. Until now, diverse means have been proven to generate iPS cells successfully in many biological species and more cell types. Meanwhile, researchers continue to target the efficiency of induction. To identify the characteristics of induced pluripotent stem cells and attest to their pluripotency, one must verify the expression of new derived stem cell genes and proteins, doubling times, methylation patterns, teratoma formation, embryoid body formation, viable chimera formation and capacity to differentiate into all cell types. In other words, induced pluripotent stem cells are theoretically similar, or even same, to natural pluripotent stem cells, for instance embryonic stem (ES) cells. Furthermore, iPS cells have the potential to take the place of ES cells ...
Pluripotent stem cells such as induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) form teratomas when transplanted into immunodeficient mice. As teratomas contain all three germ layers (endoderm, mesoderm, ectoderm), teratoma formation assay is widely used as an index of pluripotency (Evans and Kaufman, 1981; Hentze et al., 2009; Gropp et al., 2012). On the other hand, teratoma-forming tumorigenicity also represents a major risk factor impeding potential clinical applications of pluripotent stem cells (Miura et al., 2009; Okano et al., 2013). Recently, we reported that iPSCs derived from naked mole-rat lack teratoma-forming tumorigenicity when engrafted into the testes of non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice due to an ES cell-expressed Ras (ERAS) and Alternative reading frame (ARF)-dependent tumor-suppression mechanism specific to this species (Miyawaki et al., 2016). Here, we describe a method for transplanting pluripotent stem cells into the testes of
Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min for 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. ...
Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are highly expressed in embryonic stem (ES) cells, and their over-expression can induce pluripotency in both mouse and human somatic cells, indicating that these factors regulate the developmental signaling network necessary for ES cell pluripotency. However, systemic analysis of the signaling pathways regulated by Yamanaka factors has not yet been fully described. In this study, we identified the target promoters of endogenous Yamanaka factors on a whole genome scale using ChIP (chromatin immunoprecipitation)-on-chip in E14.1 mouse ES cells, and we found that these four factors co-occupied 58 promoters. Interestingly, when Oct4 and Sox2 were analyzed as core factors, Klf4 functioned to enhance the core factors for development regulation, whereas c-Myc seemed to play a distinct role in regulating metabolism. The pathway analysis revealed that Yamanaka factors collectively regulate a developmental signaling network composed of 16 developmental signaling
Epidermal grafting using cells derived from pluripotent stem cells will change the face of this side of regenerative cutaneous medicine. To date, the safety of the graft would be the major unmet deal in order to implement long-term skin grafting. In this context, experiments on large animals appear unavoidable to assess this question and possible rejection. Cellular tools for large animal models should be constructed. In this study, we generated monkey pluripotent stem cell-derived keratinocytes and evaluated their capacities to reconstruct an epidermis, in vitro as well as in vivo. Monkey pluripotent stem cells were differentiated efficiently into keratinocytes able to reconstruct fully epidermis presenting a low level of major histocompatibility complex class-I antigens, opening the way for autologous or allogeneic epidermal long-term grafting. Functional keratinocytes generated from nonhuman primate embryonic stem cells and induced pluripotent stem cells reproduce an in-vitro and in-vivo stratified
TY - JOUR. T1 - N-cadherin overexpression enhances the reparative potency of human-induced pluripotent stem cell-derived cardiac myocytes in infarcted mouse hearts. AU - Lou, Xi. AU - Zhao, Meng. AU - Fan, Chengming. AU - Fast, Vladimir G.. AU - Valarmathi, Mani T.. AU - Zhu, Wuqiang. AU - Zhang, Jianyi. N1 - Funding Information: This work was supported by the National Institute of Health (NHLBI R01 grants: HL95077, HL114120, HL131017, and UO1 HL 134764) for J.Z. Publisher Copyright: © 2019 Published on behalf of the European Society of Cardiology. All rights reserved.. PY - 2020/3/1. Y1 - 2020/3/1. N2 - Aims: In regenerative medicine, cellular cardiomyoplasty is one of the promising options for treating myocardial infarction (MI); however, the efficacy of such treatment has shown to be limited due to poor survival and/or functional integration of implanted cells. Within the heart, the adhesion between cardiac myocytes (CMs) is mediated by N-cadherin (CDH2) and is critical for the heart to ...
TY - JOUR. T1 - Generation and characterization of human induced pluripotent stem cell (hiPSC) lines from an Alzheimers disease (ASUi003-A) and non-demented control (ASUi004-A) patient homozygous for the Apolipoprotein e4 (APOE4) risk variant. AU - Brookhouser, Nicholas. AU - Zhang, Ping. AU - Caselli, Richard John. AU - Kim, Jean J.. AU - Brafman, David A.. PY - 2017. Y1 - 2017. N2 - Although the majority of late-onset Alzheimers disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene. Here, we generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi003-A] and a non-demented control (NDC) patient [ASUi004-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and ...
Title:The Role of MicroRNAs in the Pancreatic Differentiation of Pluripotent Stem Cells. VOLUME: 3 ISSUE: 1. Author(s):Natalie Francis, Melanie Moore, Guy A. Rutter and Chris Burns. Affiliation:Endocrinology Section, Biotherapeutics Department, National Institute of Biological Standards and Control, Blanche Lane, South Mimms, Hertfordshire, EN6 3QG, UK.. Keywords:Differentiation, embryonic stem cells, endoderm, induced pluripotent stem cells, insulin, microRNA, pancreas, type 1 diabetes, type 2 diabetes.. Abstract:The generation of β-cells in vitro is an attractive option for cell therapy treatments for type 1 diabetes and also for the development of more accurate disease models. A number of studies have demonstrated that insulin-expressing cells can be generated by the in vitro differentiation of human pluripotent stem cells. However, to date, these differentiation protocols are often inefficient, time-consuming and highly variable. In many cases, this is a result of an incomplete ...
Human induced pluripotent stem cells: The history and biology of human iPSCs were explored previously in Induced Pluripotent Stem Cells: A New Stem Cell Line with a Long History. In essence, iPSCs, which were first created with mouse cells in 2006 (Takahashi and Yamanaka, 2006) and then with human cells in 2007 (Yu et al., 2007; Takahashi et al., 2007), are adult cells that have been reprogrammed to an embryonic stem cell (ESC) state. This reprogramming is done by forcing adult cells to express proteins that are essential to the ESC identity (by transducing the adult cells with a retrovirus vector that contains the DNA for the key proteins). Consequently, human iPSCs look and behave nearly indistinguishably from hESCs. Like hESCs, iPSCs are pluripotent (they can become any cell type) and proliferate virtually indefinitely, both features which are important for use in regenerative medicine. However, while great improvements have been made to make this technology closer to the clinic (such as ...
Induced Pluripotent Stem Cells (iPSCs) market research report provides the details about Industry Chain structure, Market Competition, Market Size and Share, SWOT Analysis, Technology, Cost, Raw Materials, Consumer Preference, Development and Trends, Regional Forecast, Company and Profile and Product and Service.. This report includes the estimation of market size for value (million USD) and volume (K Units). Both top-down and bottom-up approaches have been used to estimate and validate the market size of Global Induced Pluripotent Stem Cells (iPSCs) market, to estimate the size of various other dependent submarkets in the overall market. Key players in the market have been identified through secondary research, and their market shares have been determined through primary and secondary research. All percentage shares, splits, and breakdowns have been determined using secondary sources and verified primary sources.. Request a Sample of Induced Pluripotent Stem Cells (iPSCs) Market Research Report ...
In 2007, two independent research groups published manuscripts that described successful genetic reprogramming of human adult somatic cells into pluripotent human stem cells.34,35 Although some technical limitations remain, this strategy suggests a promising new avenue for generating pluripotent cell lines that can inform drug development, models of disease, and ultimately, transplantation medicine. These experiments, which are discussed below, were breakthroughs because they used adult somatic cells to create pluripotent stem cells that featured hallmarks of ES cells.. In 2006, Shinya Yamanaka and colleagues at Kyoto University reported that they could use a retroviral expression vector to introduce four important stem cell factors into adult mouse cells and reprogram them to behave like ES cells (see Figure 8.3k).37 They called the reprogrammed cells iPSCs, for induced pluripotent stem cells. However, iPSCs produced using the original technique failed to produce sperm and egg cells when ...
A big breakthrough in the field of human neurodegenerative disease research to date has come in the form of induced pluripotent stem cells (iPSCs). These cells can be derived directly from patients carrying disease-causing mutations. Importantly, they also have the potential to differentiate into any cell type of the body, offering the unique opportunity to study human neurons in vitro without the need for invasive surgical techniques shedding light on the pathology of numerous neurodegenerative diseases, including several of the spinocerebellar ataxias ...
UKKi024-B Human iPS Cell Line; find Sigma-Aldrich-66540489 MSDS, related peer-reviewed papers, technical documents, similar products & more at Sigma-Aldrich.
BACKGROUND: Human-induced pluripotent stem cells (hiPSCs) are a potentially invaluable resource for regenerative medicine, including the in vitro manufacture of blood products. HiPSC-derived red blood cells are an attractive therapeutic option in hematology, yet exhibit unexplained proliferation and enucleation defects that presently preclude such applications. We hypothesised that substantial differential regulation of gene expression during erythroid development accounts for these important differences between hiPSC-derived cells and those from adult or cord-blood progenitors. We thus cultured erythroblasts from each source for transcriptomic analysis to investigate differential gene expression underlying these functional defects. RESULTS: Our high resolution transcriptional view of definitive erythropoiesis captures the regulation of genes relevant to cell-cycle control and confers statistical power to deploy novel bioinformatics methods. Whilst the dynamics of erythroid program elaboration from
Microphysiological systems (MPS) may be able to provide the pharmaceutical industry models that can reflect human physiological responses to improve drug discovery and translational outcomes. With lack of efficacy being the primary cause for drug attrition, developing MPS disease models would help researchers identify novel targets, study mechanisms in more physiologically-relevant depth, screen for novel biomarkers and test/optimize various therapeutics (small molecules, nanoparticles and biologics). Furthermore, with advances in inducible pluripotent stem cell technology (iPSC), pharmaceutical companies can access cells from patients to help recreate specific disease phenotypes in MPS platforms. Combining iPSC and MPS technologies will contribute to our understanding of the complexities of neurodegenerative diseases and of the blood brain barrier (BBB) leading to development of enhanced therapeutics. © 2018. ...
Human-induced pluripotent stem cells (hiPSCs) show a great promise as a renewable source of cells with broad biomedical applications. Since insulin has been used in the maintenance of hiPSCs, in this study we explored the role of insulin in culture of these cells. We report conditions for insulin starvation and stimulation of hiPSCs. Crystal violet staining was used to study the adhesion and proliferation of hiPSCs. Apoptosis and cell cycle assays were performed through flow cytometry. Protein arrays were used to confirm phosphorylation targets, and mRNA sequencing was used to evaluate the effect of transcriptome. Insulin improved the seeding and proliferation of hiPSCs. We also observed an altered cell cycle profile and increase in apoptosis in hiPSCs in the absence of insulin. Furthermore, we confirmed phosphorylation of key components of insulin signaling pathway in the presence of insulin and demonstrated the significant effect of insulin on regulation of the mRNA transcriptome of hiPSCs. Insulin is
This medium-ACF is a serum-free medium designed for optimal growth of human embryonic stem cells and induced pluripotent stem cells under feeder-free conditions. It is a sterile, liquid medium containing essential and non-essential amino acids, vitamins, organic and inorganic compounds, hormones, growth factors and trace minerals. The medium is bicarbonate buffered and has a pH of 7.4 when equilibrated in an incubator with an atmosphere of 5% CO2/ 95% air. This medium-ACF is formulated (quantitatively and qualitatively) to provide a defined and optimally balanced nutritional environment that selectively promotes growth of normal human embryonic stem cells and induced pluripotent stem cells in vitro. This medium should be used in conjunction with BD Matrigel™ for feeder-free culture condition ...
Recent studies have revealed negligible immunogenicity of induced pluripotent stem (iPS) cells in syngeneic mice and in autologous monkeys. Therefore, human iPS cells would not elicit immune responses in the autologous setting. However, given that human leukocyte antigen (HLA)-matched allogeneic iPS cells would likely be used for medical applications, a more faithful model system is needed to reflect HLA-matched allogeneic settings. Here we examined whether iPS cells induce immune responses in the swine leukocyte antigen (SLA)-matched setting. iPS cells were generated from the SLA-defined C1 strain of Clawn miniature swine, which were confirmed to develop teratomas in mice, and transplanted into the testes (n = 4) and ovary (n = 1) of C1 pigs. No teratomas were found in pigs on 47 to 125 days after transplantation. A Mixed lymphocyte reaction revealed that T-cell responses to the transplanted MHC-matched (C1) iPS cells were significantly lower compared to allogeneic cells. The humoral immune responses
TY - JOUR. T1 - SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation. AU - Kuroda, Takuya. AU - Yasuda, Satoshi. AU - Tachi, Shiori. AU - Matsuyama, Satoko. AU - Kusakawa, Shinji. AU - Tano, Keiko. AU - Miura, Takumi. AU - Matsuyama, Akifumi. AU - Sato, Yoji. PY - 2019/12/1. Y1 - 2019/12/1. N2 - Clinical applications of human induced pluripotent stem cells (hiPSCs) are expected, but hiPSC lines vary in their differentiation propensity. For efficient selection of hiPSC lines suitable for differentiation into desired cell lineages, here we identify SALL3 as a marker to predict differentiation propensity. SALL3 expression in hiPSCs correlates positively with ectoderm differentiation capacity and negatively with mesoderm/endoderm differentiation capacity. Without affecting self-renewal of hiPSCs, SALL3 knockdown inhibits ectoderm differentiation and conversely enhances mesodermal/endodermal differentiation. Similarly, loss- and gain-of-function ...
Induced pluripotent stem cells (iPSCs) have considerably impacted human developmental biology and regenerative medicine, notably because they circumvent the use of cells of embryonic origin and offer the potential to generate patient-specific pluripotent stem cells. However, conventional reprogramming protocols produce developmentally advanced, or primed, human iPSCs (hiPSCs), restricting their use to post-implantation human development modeling. Hence, there is a need for hiPSCs resembling preimplantation naive epiblast. Here, we develop a method to generate naive hiPSCs directly from somatic cells, using OKMS overexpression and specific culture conditions, further enabling parallel generation of their isogenic primed counterparts. We benchmark naive hiPSCs against human preimplantation epiblast and reveal remarkable concordance in their transcriptome, dependency on mitochondrial respiration and X-chromosome status. Collectively, our results are essential for the understanding of pluripotency
Induced pluripotent stem cells (iPSCs) provide a unique opportunity for generation of patient-specific cells for use in translational purposes. We aimed to compare iPSCs generated by different reprogramming methods regarding their reprogramming efficiency, pluripotency capacity, and the possibility to use high-throughput PCR-based methods for detection of human pathogenic viruses. iPSCs from skin fibroblasts (FB), peripheral blood mononuclear cells (PBMCs), or mesenchymal stem cells (MSCs) were generated by using three different reprogramming systems including chromosomal integrating and nonintegrating methods. Reprogramming efficiencies were in accordance with the literature, indicating that the parental cell type and the reprogramming method play a major role for the reprogramming efficiencies (FB: STEMCCA: |span class=inline_break||svg xmlns:xlink=http://www.w3.org/1999/xlink xmlns=http://www.w3.org/2000/svg width=32.221pt style=vertical-align:-0.3499298pt id=M1 height=8.69875pt version
Methods and Results-Transgenic hiPSC lines stably expressing a fluorescent reporter and NIS (NISpos-hiPSCs) were established. Iodide uptake, efflux, and viability of NISpos-hiPSCs were assessed in vitro. Ten (±2) days after induction of myocardial infarction by transient occlusion of the left anterior descending artery, catheter-based intramyocardial injection of NISpos-hiPSCs guided by 3-dimensional NOGA mapping was performed. Dual-isotope single photon emission computed tomographic/computed tomographic imaging was applied with the use of 123I to follow donor cell survival and distribution and with the use of 99mTC-tetrofosmin for perfusion imaging. In vitro, iodide uptake in NISpos-hiPSCs was increased 100-fold above that of nontransgenic controls. In vivo, viable NISpos-hiPSCs could be visualized for up to 15 weeks. Immunohistochemistry demonstrated that hiPSC-derived endothelial cells contributed to vascularization. Up to 12 to 15 weeks after transplantation, no teratomas were ...
TY - JOUR. T1 - A Drug Screen using Human iPSC-Derived Hepatocyte-like Cells Reveals Cardiac Glycosides as a Potential Treatment for Hypercholesterolemia. AU - Cayo, Max A.. AU - Mallanna, Sunil K.. AU - Di Furio, Francesca. AU - Jing, Ran. AU - Tolliver, Lauren B.. AU - Bures, Matthew. AU - Urick, Amanda. AU - Noto, Fallon K.. AU - Pashos, Evanthia E.. AU - Greseth, Matthew D.. AU - Czarnecki, Maciej. AU - Traktman, Paula. AU - Yang, Wenli. AU - Morrisey, Edward E.. AU - Grompe, Markus. AU - Rader, Daniel J.. AU - Duncan, Stephen A.. PY - 2017/4/6. Y1 - 2017/4/6. N2 - Efforts to identify pharmaceuticals to treat heritable metabolic liver diseases have been hampered by the lack of models. However, cells with hepatocyte characteristics can be produced from induced pluripotent stem cells (iPSCs). Here, we have used hepatocyte-like cells generated from homozygous familial hypercholesterolemia (hoFH) iPSCs to identify drugs that can potentially be repurposed to lower serum LDL-C. We found that ...
The general functions of integrins in attachment, gene expression, motility, polarity, shape, proliferation, and survival are well known. These critical functions provide reason for their wide expression across cell types. In particular, integrins are expressed in varying stem cell populations as well as other cell populations throughout the human body. Integrin alpha-6 (ITGA6) is a particular isoform of the integrin family, which is expressed across stem cell populations and has been shown to play an integral role in embryonic pluripotent stem cell self-renewal (Villa-Diaz 2016). Human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) share the same morphology and gene expression but they do not share the same origin, since hESCs are obtained from the inner cell mass of blastocyst embryos, while hiPSCs are derived from somatic cells via genetic reprogramming. This similarity is what makes hiPSCs so widely applicable to regenerative medicine as they are more ethically ...
Reprogramming factors have been used to induce pluripotent stem cells as an alternative to somatic cell nuclear transfer technology in studies targeting disease models and regenerative medicine. 3h after PHx (Fig. 6). These data were corroborated by Western Blot analysis of their protein levels (Fig. 7B &D) as well as immunohistochemical staining of these reprogramming factors after PHx (Fig. 8), both of which indicated upregulation of reprogramming factors after PHx. Peak proliferation after PHx is observed at day 1 in rats (20). Immunohistochemical staining showed that both hepatocytes and billiary cells express these factors in their nuclei. Their expression by IHC was significantly upregulated one 870281-34-8 manufacture day following PHx (Fig. 8a, b, c, and e), except for Klf4 (Fig. 8d), which is consistent with Western Blot data (Fig 7D & E). These data suggest that expression of these factors may play a role in hepatocyte proliferation and survival during liver regeneration as well. ...
Human iPSC-Derived Neural Stem Cells from a healthy male donor. Axol iPSC-Derived Neural Stem Cells can be differentiated to neurons and glial cells.
The generation of human induced pluripotent stem cells (hiPSCs) with a high differentiation potential provided a new source for hepatocyte generation not only for drug discovery and in vitro disease models, but also for cell replacement therapy. However, the reported hiPSC-derived hepatocyte-like cells (HLCs) were not well characterized and their transplantation, as the most promising clue of cell function was not reported. Here, we performed a growth factor-mediated differentiation of functional HLCs from hiPSCs and evaluated their potential for recovery of a carbon tetrachloride (CCl)-injured mouse liver following transplantation. The hiPSC-derived hepatic lineage cells expressed hepatocyte-specific markers, showed glycogen and lipid storage activity, secretion of albumin (ALB), alpha-fetoprotein (AFP), urea, and CYP450 metabolic activity in addition to low-density lipoprotein (LDL) and indocyanin green (ICG) uptake. Similar results were observed with human embryonic stem cell (hESC)-derived ...
Reprogramming of somatic cells is a valuable tool to understand the mechanisms of regaining pluripotency and further opens up the possibility of generating patient-specific pluripotent stem cells. Reprogramming of mouse and human somatic cells into pluripotent stem cells, designated as induced pluri …
The Induced Pluripotent Stem Cell (iPSC) Repository is a major effort from CIRM to create a collection of stem cells developed from thousands of individuals. CIRM is creating the iPSC bank so that scientists can use the cells, either in a petri dish or transplanted into animals, to study how disease develops and progresses and develop and test new drugs or other therapies. The iPSC bank is now open and cell lines are available at catalog.coriell.org/CIRM. The large size of the collection will provide researchers with a powerful tool for studying genetic variation between individuals, helping scientists understand how disease and treatment may vary in a diverse population like Californias. What is the iPSCRepository? How does it work? Why iPS cells? Who is generating the cells? Which diseases will be represented? How many samples are being collected for each condition? What is the iPSCRepository? The Human Induced Pluripotent Stem Cell (hiPSC) Repositoryis one of the California stem cell agencys ...
A core area of our research in the field of biodistribution of cell therapies is immunohistochemical detection of hematopoietic stem cells and induced pluripotent stem cells in tissues and whole-organ slices of laboratory animals, even if the number of cells distributed throughout the body is low. For this purpose, a broad spectrum of antibodies is established at Fraunhofer ITEM. In view of safety aspects and registration, histopathology and immunohistochemistry are performed under GLP conditions.. A risk of stem cell therapies is the formation of teratomas. These germ cell tumors can be induced by injection of pluripotent stem cells into immunodeficient mice. During tumor growth, the injected stem cells differentiate into cell types from all three germ layers, reflecting embryonic development to a certain degree. With the broad range of methods we have at our disposal, teratoma formation can be assessed as an endpoint in toxicology studies. ...
by Monya Baker. Rat pluripotent stem cells could bring knock-out rats, reprogramming insights, and a larger menagerie of stem cells.. A quartet of papers in December describe the production of rat pluripotent stem cells, both from rat embryos and from the genetic manipulation of cultured rat cells.. The rat embryonic stem cells were derived by research teams led by Austin Smith in Cambridge, UK and Qi-Long Ying of the University of Southern California, Los Angeles. They mark the first of many attempts to create ES cells that, when mixed with a normal rat embryo, can contribute to the germline in the resultant rats. Though neither team has yet produced a knockin or knockout rat, Ying believes this could happen in less than a year. The key to success was finding a combination of small molecules capable of inhibiting differentiation, which Ying and Smith described in mouse embryonic stem cells in May. While pathways to promote self-renewal in stem cells may ...
[Generation of Zone-specific Hepatocyte-like Cells from Human Induced Pluripotent Stem Cells for Accurate Prediction of Drug-induced Hepatotoxicity]. Yakugaku Zasshi. 2019;139(12):1509-1512 Authors: Mitani S Abstract Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells (iPS-HLCs) are expected to be applicable to large-scale in vitro hepatotoxicity screening...
Insulin resistance leads to a number of metabolic and cellular abnormalities including endothelial dysfunction that increase the risk of vascular disease. Although it has been particularly challenging to study the genetic determinants that predispose to abnormal function of the endothelium in insulin-resistant states, the possibility of deriving endothelial cells from induced pluripotent stem cells generated from individuals with detailed clinical phenotyping, including accurate measurements of insulin resistance accompanied by multilevel omic data (eg, genetic and genomic characterization), has opened new avenues to study this relationship. Unfortunately, several technical barriers have hampered these efforts. In the present review, we summarize the current status of induced pluripotent stem cell-derived endothelial cells for modeling endothelial dysfunction associated with insulin resistance and discuss the challenges to overcoming these limitations. ...
0007] A currently known method for purifying cardiomyocytes is by preliminarily introducing a certain marker gene (e.g. GFP) into the genome of a stem cell (Non-Patent Document 1). However, this method requires genomic alteration, which itself presents an aesthetic problem and it also involves unpredictable serious risks in safety, such as a change in cells canceration rate (Non-Patent Document 2). A method involving genomic alteration has also been reported as a way to positively remove undifferentiated pluripotent stem cells (Non-Patent Document 3). A method taking a different approach has been reported, in which ceramide analogues known to have a cell death inducing action are used to induce cell death in embryonic stem cells in a comparatively specific way (Non-Patent Document 4). However, this method does not assure satisfactory removal of pluripotent stem cells since the group of cells cultured after treatment with the ceramide analogues contained (OCT positive cells) in an amount as much ...
A consortium of 12 European partners have been awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle.. Pluripotent stem cells have the potential to generate any type of cell found in the body. They are generated and multiplied in the laboratory. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage.. The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commissions Framework 7 HEALTH research programme and Coordinated by Professor ...
The research published in the journal Nature Biotechnology shed more light on which genetic factors are critical in the reprogramming of adult skin cells to become other types of cell. In this study the researchers achieved reprogramming of adult cells without the use of a gene which has been linked to the development of tumours.. Prof Robin Lovell-Badge, Head of Developmental Genetics, MRC National Institute For Medical Research, said:. This is a very interesting follow up study from Yamanaka lab, where the main conclusion is that, of the four factors they originally used to reprogramme either mouse or human skin cells (fibroblasts) into pluripotent stem cells, the oncogene cMyc is dispensable. This is important because of their previous data showing that chimeric mice derived using iPS cells were prone to tumours, which would obviously compromise the use of human iPS cells in research and for therapies. Chimeric mice made with the 3-factor mouse iPS cells did not develop obvious tumours, ...
We studied the level of spontaneous telomere dysfunction in Rattus norvegicus (Berkenhout, 1769) (Rodentia, Muridae) embryonic fibroblasts (rEFs) and in cultured in vitro rat pluripotent stem cells (rPSCs), embryonic stem cells (rESCs) and induced pluripotent stem cells (riPSCs), on early passages and after prolonged cultivation. Among studied cell lines, rESCs showed the lowest level of telomere dysfunction, while the riPSCs demonstrated an elevated level on early passages of cultivation. In cultivation, the frequency of dysfunctional telomeres has increased in all studied cell lines; this is particularly true for dysfunctional telomeres occurring in G1 stage in riPSCs. The obtained data are mainly discussed in the connection with the specific structure of the telomere regions and their influence on the differential DNA damage response in them.
Although adipose tissue is an expandable and readily attainable source of proliferating, multipotent stem cells, its potential for use in regenerative medicine has not been extensively explored. Here we report that adult human and mouse adipose-derived stem cells can be reprogrammed to induced pluripotent stem (iPS) cells with substantially higher efficiencies than those reported for human and mouse fibroblasts. Unexpectedly, both human and mouse iPS cells can be obtained in feeder-free conditions. We discovered that adipose-derived stem cells intrinsically express high levels of pluripotency factors such as basic FGF, TGFβ, fibronectin, and vitronectin and can serve as feeders for both autologous and heterologous pluripotent cells. These results demonstrate a great potential for adipose-derived cells in regenerative therapeutics and as a model for studying the molecular mechanisms of feeder-free iPS generation and maintenance. ...
en] Dermal fibroblasts from a patient carrying a heterozygous c.88G , C mutation in the SNCA gene that encodes alpha-synuclein were reprogrammed to pluripotency by retroviruses. This pathogenic mutation generates the p.A30P form of the alpha-synuclein protein leading to autosomal dominantly inherited Parkinsons disease (PD). Two clonal iPS cell lines were generated (A30P-3 and A30P-4) and characterised by validating the silencing of viral transgenes, the expression of endogenous pluripotency genes, directed differentiation into three germ layers in-vitro and a stable molecular genotype. These iPSC lines will serve as a valuable resource in determining the role of the p.A30P SNCA mutation in PD pathogenesis ...
TY - JOUR. T1 - Pluripotent stem cells and tolerance induction in organ transplantation. AU - Imberti, Barbara. AU - Monti, Manuela. AU - Casiraghi, Federica. PY - 2015/2/21. Y1 - 2015/2/21. N2 - PURPOSE OF REVIEW: Ongoing research is constantly looking for means to modulate the immune system for long-lasting engraftment of pluripotent stem cells (PSC) during stem cell-based therapies. This study reviews data on in-vitro and in-vivo immunogenicity of embryonic and induced-PSC and describes how their immunological properties can be harnessed for tolerance induction in organ transplantation. RECENT FINDINGS: Although PSC display immunomodulatory properties in vitro, they are capable of eliciting an immune response that leads to cell rejection when transplanted into immune-competent recipients. Nevertheless, long-term acceptance of PSC-derived cells/tissues in an allogeneic environment can be achieved using minimal host conditioning. Protocols for differentiating PSC towards haematopoietic stem ...
Induced pluripotent stem cells are special because theyre not made from embryos. Instead, they come from harvesting skin cells from people, then treating those cells with genes that reverse the cells life stage back to its stem cell state. That means scientists are able to make induced pluripotent stem cells from cells taken from a patients own body. The resulting cells should be well matched to the patients own genetics, although its possible the induction part of the process introduces genetic aberrations into the cells. ...
The human cultures described here satisfy the criteria used to define pluripotent stem cells. These include presentation of a series of markers commonly used to identify pluripotent stem cells, morphological similarity to mouse ES and EG cells, normal and stable karyotype maintained over at least 10 passages, and demonstrated ability to differentiate into a wide variety of cell types.. The histological profile of these human cells (AP+, SSEA-1+, SSEA-3+, SSEA-4+, TRA-1-60+, and TRA-1-81+) differs from undifferentiated human embryonal carcinoma (EC) and rhesus ES cells, which are SSEA-1 negative (15, 38). The fact that differentiation of the human EC line NTERA2 leads to increased expression of SSEA-1 may suggest that this marker is indicative of differentiation in the human PGC-derived cultures. However, NTERA2 differentiation is accompanied by the loss of the other markers (39, 40), which we do not observe. A second possibility is that SSEA-1 reactivity reflects an intrinsic difference between ...
CAMBRIDGE, MA and SEATTLE, WA, October 3, 2017-BlueRock Therapeutics and Universal Cells Inc. today announced that they have entered into a collaboration and license agreement to create induced pluripotent stem (iPS) cell lines useful for the manufacture of allogeneic cellular therapies.. BlueRock is at the cutting edge of the cell therapy field and our collaboration with the company represents an important step in their efforts to develop off-the-shelf cell therapies for degenerative diseases, said Claudia Mitchell, Ph.D., CEO of Universal Cells. We are honored that our technology will support the advancement of BlueRocks cell therapies.. Under the terms of the agreement, BlueRock and Universal Cells will collaborate to engineer iPS cell lines for clinical use. The agreement grants BlueRock commercial rights to use the engineered cell lines for undisclosed therapeutic applications.. This partnership with Universal Cells provides us with an important technology useful to advance ...
Latest publications. Shinya Yamanaka, MD, PhD - Fujishiro SH, Nakano K, Mizukami Y, Azami T, Arai Y, Matsunari H, Ishino R, Nishimura T, Watanabe M, Abe T, Furukawa Y, Umeyama K, Yamanaka S, Ema M, Nagashima H, Hanazono Y. Generation of Naive-like Porcine Induced Pluripotent Stem Cells Capable of Contributing to Embryonic and Fetal Development. Stem Cells Dev. 2012 Aug 13; Shinya Yamanaka, MD, PhD - Blanpain C, Daley GQ, Hochedlinger K, Passegue E, Rossant J, Yamanaka S. (2012) Stem cells assessed. Nat Rev Mol Cell Biol 13: 471-6; Shinya Yamanaka, MD, PhD - Tanaka T, Takahashi K, Yamane M, Tomida S, Nakamura S, Oshima K, Niwa A, Nishikomori R, Kambe N, Hara H, Mitsuyama M, Morone N, Heuser JE, Yamamoto T, Watanabe A, Sato-Otsubo A, Ogawa S, Asaka I, Heike T, Yamanaka S, Nakahata T, Saito MK. Induced pluripotent stem cells from CINCA syndrome patients as a model for dissecting somatic mosaicism and drug discovery. Blood. 2012 Aug 9; 120(6):1299-308; Shinya Yamanaka, MD, PhD - Isobe H, Shoji M, ...
Looking for online definition of induced pluripotent stem cell in the Medical Dictionary? induced pluripotent stem cell explanation free. What is induced pluripotent stem cell? Meaning of induced pluripotent stem cell medical term. What does induced pluripotent stem cell mean?
TY - JOUR. T1 - Epigenetic Silencing of the Key Antioxidant Enzyme Catalase in Karyotypically Abnormal Human Pluripotent Stem Cells. AU - Konki, Mikko. AU - Pasumarthy, Kalyan. AU - Malonzo, Maia. AU - Sainio, Annele. AU - Valensisi, Cristina. AU - Söderström, Mirva. AU - Emani, Maheswara Reddy. AU - Stubb, Aki. AU - Närvä, Elisa. AU - Ghimire, Bishwa. AU - Laiho, Asta. AU - Järveläinen, Hannu. AU - Lahesmaa, Riitta. AU - Lähdesmäki, Harri. AU - Hawkins, R. David. AU - Lund, Riikka J.. PY - 2016/2/25. Y1 - 2016/2/25. N2 - Epigenomic regulation is likely to be important in the maintenance of genomic integrity of human pluripotent stem cells, however, the mechanisms are unknown. We explored the epigenomes and transcriptomes of human pluripotent stem cells before and after spontaneous transformation to abnormal karyotypes and in correlation to cancer cells. Our results reveal epigenetic silencing of Catalase, a key regulator of oxidative stress and DNA damage control in abnormal cells. Our ...
TY - JOUR. T1 - A fully defined and scalable 3D culture system for human pluripotent stem cell expansion and differentiation. AU - Lei, Yuguo. AU - Schaffer, David V.. PY - 2013/12/24. Y1 - 2013/12/24. N2 - Human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, are promising for numerous biomedical applications, such as cell replacement therapies, tissue and whole-organ engineering, and high-throughput pharmacology and toxicology screening. Each of these applications requires large numbers of cells of high quality; however, the scalable expansion and differentiation of hPSCs, especially for clinical utilization, remains a challenge. We report a simple, defined, efficient, scalable, and good manufacturing practice-compatible 3D culture system for hPSC expansion and differentiation. It employs a thermoresponsive hydrogel that combines easy manipulation and completely defined conditions, free of any human- or animal-derived factors, and ...
TY - JOUR. T1 - Brief report. T2 - Efficient generation of hematopoietic precursors and progenitors from human pluripotent stem cell lines. AU - Woods, Niels Bjarne. AU - Parker, Aaron S.. AU - Moraghebi, Roksana. AU - Lutz, Margaret K.. AU - Firth, Amy L.. AU - Brennand, Kristen J.. AU - Berggren, W. Travis. AU - Raya, Angel. AU - Izpisua Belmonte, Juan Carlos. AU - Gage, Fred H.. AU - Verma, Inder M.. PY - 2011/1/1. Y1 - 2011/1/1. N2 - By mimicking embryonic development of the hematopoietic system, we have developed an optimized in vitro differentiation protocol for the generation of precursors of hematopoietic lineages and primitive hematopoietic cells from human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSCs). Factors such as cytokines, extra cellular matrix components, and small molecules as well as the temporal association and concentration of these factors were tested on seven different human ESC and iPSC lines. We report the differentiation of up to 84% human CD45+ ...
Functional cardiomyocytes can be efficiently derived from human pluripotent stem cells (hPSCs), which collectively include embryonic and induced pluripotent stem cells. This cellular platform presents
TY - JOUR. T1 - Suppression of histone deacetylation promotes the differentiation of human pluripotent stem cells towards neural progenitor cells. AU - Yang, Juan. AU - Tang, Yu. AU - Liu, Hui. AU - Guo, Fang. AU - Ni, Jun. AU - Le, Weidong. PY - 2014. Y1 - 2014. N2 - Background: Emerging studies of human pluripotent stem cells (hPSCs) raise new prospects for neurodegenerative disease modeling and cell replacement therapies. Therefore, understanding the mechanisms underlying the commitment of neural progenitor cells (NPCs) is important for the application of hPSCs in neurodegenerative disease therapies. It has been reported that epigenetic modifications of histones play important roles in neural differentiation, but the exact mechanisms in regulating hPSC differentiation towards NPCs are not fully elucidated. Results: We demonstrated that suppression of histone deacetylases (HDACs) promoted the differentiation of hPSCs towards NPCs. Application of HDAC inhibitors (HDACi) increased the expression ...
TY - JOUR. T1 - Defining early hematopoietic-fated primitive streak specification of human pluripotent stem cells by the orchestrated balance of Wnt, activin, and BMP signaling. AU - Shen, Jun. AU - Lyu, Cuicui. AU - Zhu, Yaoyao. AU - Feng, Zicen. AU - Zhang, Shuo. AU - Hoyle, Dixie L.. AU - Ji, Guangzhen. AU - Brodsky, Robert A. AU - Cheng, Tao. AU - Wang, Zack Z.. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Distinct regions of the primitive streak (PS) have diverse potential to differentiate into several tissues, including the hematopoietic lineage originated from the posterior region of PS. Although various signaling pathways have been identified to promote the development of PS and its mesoderm derivatives, there is a large gap in our understanding of signaling pathways that regulate the hematopoietic fate of PS. Here, we defined the roles of Wnt, activin, and bone morphogenetic protein (BMP) signaling pathways in generating hematopoietic-fated PS from human pluripotent stem cells (hPSCs). We found ...
en] Human pluripotent stem cells, including embryonic (hES) and induced pluripotent stem cells (hiPS), retain the ability to self-renew indefinitely, while maintaining the capacity to differentiate into all cell types of the nervous system. While human pluripotent cell-based therapies are unlikely to arise soon, these cells can currently be used as an inexhaustible source of committed neurons to perform high-throughput screening and safety testing of new candidate drugs. Here, we describe critically the available methods and molecular factors that are used to direct the differentiation of hES or hiPS into specific neurons. In addition, we discuss how the availability of patient-specific hiPS offers a unique opportunity to model inheritable neurodegenerative diseases and untangle their pathological mechanisms, or to validate drugs that would prevent the onset or the progression of these neurological disorders ...
hPSC lines used in this work included H9 (WA09, P50, and P54; WiCell), H7 (WA07, P52; WiCell), and 1196a (a distinct iPSC line, P42; UM Pluripotent Stem Cell Core). All work with all of these hPSC lines was preapproved by the Human Pluripotent Stem Cell Research Oversight Committee at the University of Michigan. All cell lines have been maintained in a feeder-free system for at least 10 passages and were karyotypically normal at the indicated passage. Karyotype analysis was performed at Cell Line Genetics. These cells are frequently tested for pluripotency markers and differentiation ability. All cell lines tested negative for mycoplasma contamination (LookOut Mycoplasma PCR Detection kit; Sigma-Aldrich). The mESC line E14Tg2a.4 was obtained from the UM Transgenic Core (originally generated by A. Smith; Hooper et al., 1987), and mEpiSCs (22M) were generated in the laboratory of SK as previously described (Tesar et al., 2007) by culturing pre- and peri-implantation embryos on inactivated mouse ...
Large-scale culture of human pluripotent stem cells (PSCs), including embryonic (ESCs) and induced pluripotent stem cells (iPSCs), will be
The cerebellar ataxias are a group of incurable brain disorders that are caused primarily by the progressive dysfunction and degeneration of cerebellar Purkinje cells. The lack of reliable disease models for the heterogeneous ataxias has hindered the understanding of the underlying pathogenic mechanisms as well as the development of effective therapies for these devastating diseases. Recent advances in the field of induced pluripotent stem cell (iPSC) technology offer new possibilities to better understand and potentially reverse disease pathology. Given the neurodevelopmental phenotypes observed in several types of ataxias, iPSC-based models have the potential to provide significant insights into disease progression, as well as opportunities for the development of early intervention therapies. To date, however, very few studies have successfully used iPSC-derived cells to model cerebellar ataxias. In this review, we focus on recent breakthroughs in generating human iPSC-derived Purkinje cells. We also
Laminin α5 substrates promote survival, network formation and functional development of human pluripotent stem cell-derived neurons in ...
The Japanese Patent Office has granted the first patent for induced pluripotent stem cells (iPS cells) to Kyoto University, where researcher Shinya Yamanaka produced both the first non-human iPS cells in 2006 and, using the same process, the first human iPS cells in 2007.The Japanese patent, a limited version of a much broader international patent application covering all forms of iPS cell (excluding germ cells) across all species, covers only human iPS cells created using Yamanakas process based on reprogramming adult cells using four gene factors.. The granting of the patent in Japan was fast-tracked by Patent Office officials so as to make clear the Universitys claim while the broader patent goes through lengthy processing across the worlds other major patent institutions. The urgency in part reflects the contemporaneous progress of a US team headed by James Thomson at the University of Wisconsin which published its own successes in producing human iPS cells on the same day as Yamanaka in ...
Pluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date include embryonic stem (ES) and induced pluripotent stem (iPS) cells. ES cells are derived from the inner cell mass (ICM) of blastocyst-stage embryos. iPS cells are generated by reprogramming somatic cells back to pluripotent state with defined reprogramming factors, Oct4, Sox2, Klf4 and c-Myc (also known as Yamanaka factors). PSCs including ES cells and iPS cells are categorized into two groups by their morphology, gene expression profile and external signal dependence. Conventional mouse-type ES/iPS cells are called naive state cells. They are mainly maintained under the control of LIF and BMP signaling. On the other hand, human-type ES/iPS cells, which are in need of Activin and FGF signaling, are termed primed state. However, these signaling pathways converge towards the activation of a core ...
Although there are no specific restrictions in the NIH Intramural Research Program (IRP) with regard to acquiring or sending out human induced pluripotent stem (iPS) cell lines, there are relevant requirements in the NIH guidelines on human embryonic stem cells that apply to potential uses of human iPS cell Lines. Specifically:
|jats:p|Induced pluripotent stem cell (iPSC) technology has emerged as an important tool in understanding, and potentially reversing, disease pathology. This is particularly true in the case of neurodegenerative diseases, in which the affected cell types are not readily accessible for study. Since the first descriptions of iPSC-based disease modelling, considerable advances have been made in understanding the aetiology and progression of a diverse array of neurodegenerative conditions, including Parkinsons disease and Alzheimers disease. To date, however, relatively few studies have succeeded in using iPSCs to model the neurodegeneration observed in cerebellar ataxia. Given the distinct neurodevelopmental phenotypes associated with certain types of ataxia, iPSC-based models are likely to provide significant insights, not only into disease progression, but also to the development of early-intervention therapies. In this review, we describe the existing iPSC-based disease models of this heterogeneous
TY - JOUR. T1 - Development of genetic quality tests for good manufacturing practice-compliant induced pluripotent stem cells and their derivatives. AU - Jo, Hye Yeong. AU - Han, Hyo Won. AU - Jung, Inuk. AU - Ju, Ji Hyeon. AU - Park, Soon Jung. AU - Moon, Sunghwan. AU - Geum, Dongho. AU - Kim, Hyemin. AU - Park, Han Jin. AU - Kim, Sun. AU - Stacey, Glyn N.. AU - Koo, Soo Kyung. AU - Park, Mi Hyun. AU - Kim, Jung Hyun. N1 - Funding Information: This work was supported by the Korea National Institute of Health Intramural Research Program 4800-4861-312-210-13 (grant nos. 2017-NG61003-00, 2017-NG61004-00, 2020-NG-018-00 and 2020-NG-019-00).. PY - 2020/12/1. Y1 - 2020/12/1. N2 - Although human induced pluripotent stem cell (hiPSC) lines are karyotypically normal, they retain the potential for mutation in the genome. Accordingly, intensive and relevant quality controls for clinical-grade hiPSCs remain imperative. As a conceptual approach, we performed RNA-seq-based broad-range genetic quality tests ...
TY - JOUR. T1 - CXCR2 and its related ligands play a novel role in supporting the pluripotency and proliferation of human pluripotent stem cells. AU - Jung, Ji Hye. AU - Lee, Seung Jin. AU - Kim, Jihea. AU - Lee, Songhee. AU - Sung, Hwa Jung. AU - An, Jungsuk. AU - Park, Yong. AU - Kim, Byung Soo. PY - 2015/4/15. Y1 - 2015/4/15. N2 - Basic fibroblast growth factor (bFGF) is a crucial factor sustaining human pluripotent stem cells (hPSCs). We designed this study to search the substitutive factors other than bFGF for the maintenance of hPSCs by using human placenta-derived conditioned medium without exogenous bFGF (hPCCM-), containing chemokine (C-X-C motif) receptor 2 (CXCR2) ligands, including interleukin (IL)-8 and growth-related oncogene α (GROα), which were developed on the basis of our previous studies. First, we confirmed that IL-8 and/or GROα play independent roles to preserve the phenotype of hPSCs. Then, we tried CXCR2 blockage of hPSCs in hPCCM- and verified the significant decrease ...
TY - JOUR. T1 - Gingival Fibroblasts as Autologous Feeders for Induced Pluripotent Stem Cells. AU - Yu, G.. AU - Okawa, H.. AU - Okita, K.. AU - Kamano, Y.. AU - Wang, F.. AU - Saeki, M.. AU - Yatani, H.. AU - Egusa, H.. PY - 2016/1/1. Y1 - 2016/1/1. N2 - Human gingival fibroblasts (hGFs) present an attractive source of induced pluripotent stem cells (iPSCs), which are expected to be a powerful tool for regenerative dentistry. However, problems to be addressed prior to clinical application include the use of animal-derived feeder cells for cultures. The aim of this study was to establish an autologous hGF-derived iPSC (hGF-iPSC) culture system by evaluating the feeder ability of hGFs. In both serum-containing and serum-free media, hGFs showed higher proliferation than human dermal fibroblasts (hDFs). Three hGF strains were isolated under serum-free conditions, although 2 showed impaired proliferation. When hGF-iPSCs were transferred onto mitomycin C-inactivated hGFs, hDFs, or mouse-derived SNL ...
Generation of functional eggs from pluripotent stem cells in culture would have impacts on reproductive biology and regenerative medicine. We have recently established a novel culture system in which mouse pluripotent stem cells differentiate to mature oocytes in a manner similar to oogenesis in ...
Culture conditions play an important role in regulating the genomic integrity of Human Pluripotent Stem Cells (HPSCs). We report that HPSCs cultured in Essential 8 (E8) and mTeSR, two widely used media for feeder-free culturing of HPSCs, had many fold higher levels of ROS and higher mitochondrial potential than cells cultured in Knockout Serum Replacement containing media (KSR). HPSCs also exhibited increased levels of 8-hydroxyguanosine, phospho-histone-H2a.X and p53, as well as increased sensitivity to γ-irradiation in these two media. HPSCs in E8 and mTeSR had increased incidence of changes in their DNA sequence, indicating genotoxic stress, in addition to changes in nucleolar morphology and number. Addition of antioxidants to E8 and mTeSR provided only partial rescue. Our results suggest that it is essential to determine cellular ROS levels in addition to currently used criteria i.e. pluripotency markers, differentiation into all three germ layers and normal karyotype through multiple ...
BioMed Research International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies covering a wide range of subjects in life sciences and medicine. The journal is divided into 55 subject-specific sections.
The generation of human induced pluripotent stem cells (hiPSCs) represents an exciting advancement with promise for stem cell transplantation therapies as well as for neurological disease modeling. Based on the emerging roles for astrocytes in neurological disorders, we investigated whether hiPSC-derived astrocyte progenitors could be engrafted to the rodent spinal cord and how the characteristics of these cells changed between in vitro culture and after transplantation to the in vivo spinal cord environment. Our results show that human embryonic stem cell- and hiPSC-derived astrocyte progenitors survive long-term after spinal cord engraftment and differentiate to astrocytes in vivo with few cells from other lineages present. Gene profiling of the transplanted cells demonstrates the astrocyte progenitors continue to mature in vivo and upregulate a variety of astrocyte-specific genes. Given this mature astrocyte gene profile, this work highlights hiPSCs as a tool to investigate disease-related ...
TY - JOUR. T1 - Tumorigenic development of induced pluripotent stem cells in ischemic mouse brain. AU - Yamashita, Toru. AU - Kawai, Hiromi. AU - Tian, Fengfeng. AU - Ohta, Yasuyuki. AU - Abe, Koji. N1 - Copyright: Copyright 2012 Elsevier B.V., All rights reserved.. PY - 2011. Y1 - 2011. N2 - Induced pluripotent stem (iPS) cells may provide cures for various neurological diseases. However, undifferentiated iPS cells have high tumorigenicity, and evaluation of the cells fates, especially in pathologic condition model, is needed. In this study, we demonstrated the effect of ischemic condition to undifferentiated iPS cells fates in a mouse model of transient middle cerebral artery occlusion (MCAO). Undifferentiated iPS cells were characterized with immunofluorescent staining. The iPS cells (5 ×10 5) were injected into ipsilateral striatum and cortex after 24 h of MCAO. Histological analysis was performed from 3 to 28 days after cell transplantation. iPS cells in ischemic brain formed teratoma with ...
The capability to reprogram somatic cells to induced pluripotent stem cells (iPSCs) has revolutionized the field of regenerative medicine. iPSC and ESC lines, between different passages of Clioquinol the same iPSC line, and even between Clioquinol different populations at a specific passage of the same iPSC line. Such variations potentially affect the properties of iPSCs and undermine their accountability in downstream applications. In this Perspective, we discuss the genetic and epigenetic variations in iPSCs and their causes, the implications of these variations in iPSC applications, and potential approaches to cope with these variations. Genetic variations in iPSCs An iPSC genome may harbor a wide range of variations, including aneuploidy, subchromosomal copy number variation (CNV), and single nucleotide variations (SNVs). These variations can be introduced into the iPSCs from different sources during iPSC generation and maintenance (Physique 1). First, genetic variations in iPSCs may ...
Recorded during the ISSCR 2017 Innovation Showcase in Boston, this tutorial highlights human pluripotent stem cell (hPSC) gene-editing and cardiac differentiation workflows using the CloneR™ supplement and the STEMdiff™ Cardiomyocyte System. This talk is
Page citation: NIH Human Pluripotent Stem Cell Registry . In Stem Cell Information [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2008 [cited Tuesday, January 13, 2009] Available at ,http://stemcells.nih.gov/research/registry/defaultpage, ...
Heng, J.-C.D., Loh, K.M., Ng, H.-H. (2012-01). Investigating the bona fide differentiation capacity of human pluripotent stem cells. Cell Research 22 (1) : 6-8. ScholarBank@NUS Repository. https://doi.org/10.1038/cr. ...
Since the first discovery that human pluripotent stem cells (hPS cells) can differentiate to cardiomyocytes, efforts have been made to optimize the conditions under which this process occurs
A lot of optimism and promise surrounds the use of human pluripotent stem cells (hPSCs) for applications in regenerative medicine and drug discovery. However, technical challenges still hamper the culturing and differentiation ...
TY - JOUR. T1 - Autonomous and Non-autonomous Defects Underlie Hypertrophic Cardiomyopathy in BRAF-Mutant hiPSC-Derived Cardiomyocytes. AU - Josowitz, Rebecca. AU - Mulero-Navarro, Sonia. AU - Rodriguez, Nelson A.. AU - Falce, Christine. AU - Cohen, Ninette. AU - Ullian, Erik M.. AU - Weiss, Lauren A.. AU - Rauen, Katherine A. AU - Sobie, Eric A.. AU - Gelb, Bruce D.. PY - 2016/9/13. Y1 - 2016/9/13. N2 - Germline mutations in BRAF cause cardio-facio-cutaneous syndrome (CFCS), whereby 40% of patients develop hypertrophic cardiomyopathy (HCM). As the role of the RAS/MAPK pathway in HCM pathogenesis is unclear, we generated a human induced pluripotent stem cell (hiPSC) model for CFCS from three patients with activating BRAF mutations. By cell sorting for SIRPα and CD90, we generated a method to examine hiPSC-derived cell type-specific phenotypes and cellular interactions underpinning HCM. BRAF-mutant SIRPα+/CD90− cardiomyocytes displayed cellular hypertrophy, pro-hypertrophic gene expression, ...
Read Expression patterns of germ line specific genes in mouse and human pluripotent stem cells are associated with regulation of ground and primed state of pluripotency, Russian Journal of Developmental Biology on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Dr. Chad Cowan discusses his research efforts to understand metabolic disease using the CRISPR/Cas system in human pluripotent stem cells to create genetic disease models
Chromatin architecture has been implicated in cell type-specific gene regulatory programs, yet how chromatin remodels during development remains to be fully elucidated. Here, by interrogating chromatin reorganization during human pluripotent stem cell (hPSC) differentiation, we discover a role for t …
Focal adhesions are known as signalling platforms broadcasting the information of the biochemical and physical qualities of the extracellular matrix into intracellular signalling cascades. However, focal adhesions remain unstudied in the context of human pluripotent stem cells. The research group led by Academy Professor Johanna Ivaska from the Turku Bioscience Centre at the University of Turku unveiled the ultrastructure of focal adhesion scaffold using state-of-the-art super-resolution microscopy in collaboration with the world-renowned Howard Hughes Medical Institutes Janelia Research Campus.
Here, we present human pluripotent stem cell (hPSC) culture protocols, based on non-colony type monolayer (NCM) growth of dissociated...
TY - JOUR. T1 - Establishment of a Duchenne muscular dystrophy patient-derived induced pluripotent stem cell line carrying a deletion of exons 51-53 of the dystrophin gene (CCMi003-A). AU - Rovina, D.. AU - Castiglioni, E.. AU - Farini, A.. AU - Bellichi, M.. AU - Gervasini, C.. AU - Paganini, S.. AU - Di Segni, M.. AU - Santoro, R.. AU - Torrente, Y.. AU - Pompilio, G.. AU - Gowran, A.. N1 - Export Date: 6 February 2020. PY - 2019. Y1 - 2019. U2 - 10.1016/j.scr.2019.101544. DO - 10.1016/j.scr.2019.101544. M3 - Article. VL - 40. JO - Stem Cell Research. JF - Stem Cell Research. SN - 1873-5061. ER - ...
Biomedicum stem cell centre (BSCC) core facility is a comprehensive provider of human pluripotent stem cell services at the Meilahti campus of the University of Helsinki. Human induced pluripotent stem cell (hiPSC)-derived disease specific cell models, coupled with the progress in genome editing technology, serve as an opportunity to study pathophysiological mechanisms in disease-relevant cell models. We provide locally derived human pluripotent stem cell lines (hPSC), genome editing, and generation of hiPSC lines from somatic cells provided by the client. BSCC operates on a fee-for-service basis in providing custom hiPSC derivation and generation of hPSC knockout lines using the latest technologies.. 1. Cell and reporter lines distribution Human embryonic stem cells (hESC) and hiPSC derived locally are provided upon request. We can also provide OCT4 and SOX2 reporter hiPSC lines. Follow this procedure:. ...
Human induced pluripotent stem cells (hiPSC) have enabled a major step forward in pathophysiologic studies of inherited diseases and may also prove to be valuable in in vitro drug testing. Long QT syndrome (LQTS), characterized by prolonged cardiac repolarization and risk of sudden death, may be inherited or result from adverse drug effects. Using a microelectrode array platform, we investigated the effects of six different drugs on the electrophysiological characteristics of human embryonic stem cell-derived cardiomyocytes as well as hiPSC-derived cardiomyocytes from control subjects and from patients with type 1 (LQT1) and type 2 (LQT2) of LQTS. At baseline the repolarization time was significantly longer in LQTS cells compared to controls. Isoprenaline increased the beating rate of all cell lines by 10-73 % but did not show any arrhythmic effects in any cell type. Different QT-interval prolonging drugs caused prolongation of cardiac repolarization by 3-13 % (cisapride), 10-20 % ...
Huntingtons disease results in massive loss of cells in the brain, particularly in regions called the cortex and striatum. The cells depicted are from a patient with Huntingtons disease that have been genetically corrected. They are striatal neurons with expression of DARPP-32 and beta-III-tubulin, markers of neurons lost in Huntingtons disease.. June 28, 2012 Novato, California Researchers at the Buck Institute have corrected the genetic mutation responsible for Huntingtons disease (HD) using a human induced pluripotent stem cell (iPSC) that came from a patient suffering from the incurable, inherited neurodegenerative disorder. Scientists took the diseased iPSCs, made the genetic correction, generated neural stem cells and then transplanted the mutation-free cells into a mouse model of HD where they are generating normal neurons in the area of the brain affected by HD. Results of the research are published in the June 28, 2012 online edition of the journal Cell Stem Cell.. iPSCs are ...
In a recent study, researchers used our MEA chip cell-culture system to culture the hiPSC-Derived Sensory Neuron Progenitors, along with our Sensory Neuron Maintenance Medium and coating reagents. The study also used our step-by-step guideline to help with the set up and maintenance of the cell-culture itself, along with our MEA system guideline to assist with culturing the hiPSC-Derived Sensory Neuron Progenitors on an MEA system. One key part of the protocol in particular, is to remove the non-neuronal population. This ensures a more homogeneous population of sensory neurons and is simple to do with the addition of mitomycin C to the Sensory Neuron Maintenance Medium after two days of culture. You should see the full effects of growth arrest after seven days. The hiPSC-Derived Sensory Neuron Progenitors must then be maintained in the Sensory Neuron Maintenance Medium (containing growth factors Glial-Derived Neurotrophic Factor (GDNF), Nerve Growth Factor (NGF), Brain-Derived Neurotrophic ...
Influence of Donor Age on Induced Pluripotent Stem Cells To explore the impact of age on iPSC quality, investigators produced induced pluripotent stem cells (iPSCs) from blood cells of 16 donors aged 21-100. They found that iPSCs from older donors retain an epigenetic signature of age, which can be reduced through passaging. Clonal expansion via reprogramming also enables the discovery of somatic mutations present in individual donor cells, which are missed by bulk sequencing methods. [Nat Biotechnol] Abstract Self-Organized Amniogenesis by Human Pluripotent Stem Cells in a Biomimetic Implantation-Like Niche Scientists report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. They showed that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical ...
Non-viral transfection of mammalian cardiomyocytes (CMs) is challenging. The current study aims to characterize and determine the non-viral vector based gene transfection efficiency with human induced pluripotent stem cells (hiPSCs) derived cardiomyocytes (hiPSC-CMs). hiPSC-CMs differentiated from PCBC hiPSCs were used as a cell model to be transfected with plasmids carrying green fluorescence protein (pGFP) using polyethylenimine (PEI), including Transporter 5 Transfection Reagent (TR5) and PEI25, and liposome, including lipofectamine-2000 (Lipo2K), lipofectamine-3000 (Lipo3K), and Lipofectamine STEM (LipoSTEM). The gene transfection efficiency and cell viability were quantified by flow cytometry. We found that the highest gene transfection efficiency in hiPSC-CMs on day 14 of contraction can be achieved by LipoSTEM which was about 32.5 ± 6.7%. However, it also cuased poor cell viability (60.1 ± 4.5%).. Furthermore, a prolonged culture of (transfection on day 23 of contraction) hiPSC-CMs not ...
In this application note from Miltenyi, neural differentiation towards either neural crest (NC) or neural stem cells (NSC) is optimised. A magnetic cell separation protocol to standardise quality and number of true pluripotent stem cells before inducing neural differentiation is developed.