Showing papers by "Peter W. Andrews published in 2011"
University of Sheffield1, Newcastle upon Tyne Hospitals NHS Foundation Trust2, Agency for Science, Technology and Research3, Royan Institute4, Stanford University5, Boston Children's Hospital6, University of Nottingham7, University of Southern California8, Hebrew University of Jerusalem9, Tel Aviv Sourasky Medical Center10, Cedars-Sinai Medical Center11, University of Geneva12, Manchester Academic Health Science Centre13, University of Manchester14, Genome Institute of Singapore15, Seoul National University16, Harvard University17, University of Edinburgh18, Masaryk University19, WiCell20, University of São Paulo21, Central South University22, University College London23, Karolinska Institutet24, Jawaharlal Nehru Centre for Advanced Scientific Research25, Kyoto University26, Shanghai Jiao Tong University27, Kurchatov Institute28, Russian Academy of Sciences29, Vrije Universiteit Brussel30, King's College London31, Leiden University32, University of Helsinki33, Yale University34, Hospital for Sick Children35, University of New South Wales36, University of Tampere37, Commonwealth Scientific and Industrial Research Organisation38
TL;DR: Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells, and single-nucleotide polymorphism analysis revealed that they included representatives of most major ethnic groups.
Abstract: The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells.
506 citations
University of Liverpool1, AstraZeneca2, Hebrew University of Jerusalem3, Cedars-Sinai Medical Center4, University of Sheffield5, Manchester Academic Health Science Centre6, Novartis7, Carnegie Learning8, Medicines and Healthcare Products Regulatory Agency9, ReNeuron10, Paul Ehrlich Institute11, Pfizer UK12
TL;DR: The safety issues pertaining to novel stem cell-derived treatments are set out, knowledge gaps that require further research are identified, and a roadmap for developing safety assessment criteria is suggested.
211 citations
TL;DR: This work shows that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing this barrier, and it is mediated by signalling through gap junction proteins following the generation of mitochondrial free radicals.
Abstract: The use of nanoparticles in medicine is ever increasing, and it is important to understand their targeted and non-targeted effects We have previously shown that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing this barrier Here, we show that this indirect DNA damage depends on the thickness of the cellular barrier, and it is mediated by signalling through gap junction proteins following the generation of mitochondrial free radicals Indirect damage was seen across both trophoblast and corneal barriers Signalling, including cytokine release, occurred only across bilayer and multilayer barriers, but not across monolayer barriers Indirect toxicity was also observed in mice and using ex vivo explants of the human placenta If the importance of barrier thickness in signalling is a general feature for all types of barriers, our results may offer a principle with which to limit the adverse effects of nanoparticle exposure and offer new therapeutic approaches
114 citations
TL;DR: The loss of induction of alphafetoprotein in the culture-adapted cells was especially marked, suggesting that they had a reduced capacity to produce extra-embryonic endoderm, and may contribute to the growth advantages of genetically variant cells.
Abstract: Upon prolonged culture, human embryonic stem (hES) cells undergo adaptation, exhibiting decreased population doubling times and increased cloning efficiencies, often associated with karyotypic changes. To test whether culture adaptation influences the patterns of differentiation of hES cells, we compared the expression of genes indicative of distinct embryonic lineages in the embryoid bodies produced from two early passage, karyotypically normal hES cell lines, and two late passage, karyotypically abnormal hES cell lines. One of the abnormal lines was a subline of one of the normal early passage lines. The embryoid bodies from each of the lines showed evidence of extensive differentiation. However, there were differences in the expression of several genes, indicating that the culture adapted hES cells show altered patterns of differentiation compared to karyotypically normal hES cells. The loss of induction of alphafetoprotein in the culture-adapted cells was especially marked, suggesting that they had a reduced capacity to produce extra-embryonic endoderm. These changes may contribute to the growth advantages of genetically variant cells, not only by reflecting an increased tendency to self renewal rather than to differentiate, but also by reducing spontaneous differentiation to derivatives that themselves may produce factors that could induce further differentiation of undifferentiated stem cells.
38 citations
TL;DR: Pinacidil has been used for many years as a vasodilator drug to treat hypertension and its manufacture and traceability are well defined and it is also considerably cheaper than Y-27632, so the use of pinacidil offers an efficient method for recovery of cryopreserved dissociated human ES cells.
24 citations
TL;DR: Functional testing of single cells has shown that undifferentiated ES cells can be segregated into functionally discrete subpopulations on the basis of SSEA3 expression, suggesting that ES cells with pluripotent/self-renewal capacities can exhibit different responses to induction of differentiation.
21 citations
TL;DR: An image-based screening assay is developed to identify compounds that affect survival or differentiation of the human EC stem cell line NTERA2 by measuring the effect on cell number and the proportion of cells expressing a pluripotency-associated marker SSEA3.
Abstract: Disentangling the complex interactions that govern stem cell fate choices of self-renewal, differentiation, or death presents a formidable challenge. Image-based phenotype-driven screening meets th...
16 citations
TL;DR: The authors' data reveal a range of reactivity for all antibodies against both ES and EC cells, suggesting that these markers will afford recognition of unique sub-states within the undifferentiated stem cell compartment.
Abstract: Summary
The antigenic profile of human embryonic stem (ES) and embryonal carcinoma (EC) cells has served as a key element of their characterization, with a common panel of surface and intracellular markers now widely used. Such markers have been used to identify cells within the ‘undifferentiated state’, yet it appears that this categorization may be an oversimplification, because a number of sub-states appear to exist within this state. To increase the resolution of the undifferentiated state, we have generated eight novel monoclonal antibodies, all capable of recognizing undifferentiated human ES and EC cells, and herein describe their characterization. The reactivity of these antibodies against a range of cell lines is reported, as well as their developmental regulation, basic biochemistry and reactivity in immunohistochemistry of testicular germ cell tumours. Our data reveal a range of reactivity for all antibodies against both ES and EC cells, suggesting that these markers will afford recognition of unique sub-states within the undifferentiated stem cell compartment.
14 citations
TL;DR: A newly identified surface marker on human embryonic stem cells allows rare tumor-forming cells to be removed from preparations of differentiated cells.
Abstract: A newly identified surface marker on human embryonic stem cells allows rare tumor-forming cells to be removed from preparations of differentiated cells.
13 citations
01 Jan 2011
TL;DR: The origins of the cancer stem cell concept, issues that need to be addressed to enhance its utility for developing methods for preventing and treating cancer, and the possibility that a tumor can be composed entirely of oxymoronic nullipotent stem cells are considered.
Abstract: The cancer stem cell hypothesis has become popular in the past few years, in part to provide an explanation of the recurrence of the disease following initial remission and apparent cure. Nevertheless, the concept that cancer is a developmental disease resulting from aberrant control of cellular differentiation is old and is epitomized by teratocarcinomas, a form of testicular germ cell tumor, and by the hematological malignancies. These ideas have developed in parallel with the notion of tissue stem cells that provide for the replacement of functional cells in adult tissues, especially in those tissues subject to continual ‘wear and tear’ throughout adult life. Although a simple view might hold that cancers contain a small population of cancer initiating stem cells equivalent to and, perhaps, derived from the stem cells of the tissue from which they arise, the circumstances of such cancer stem cells is inevitably very different from those of tissue stem cells. Consequently the possibility that a tumor can be composed entirely of oxymoronic nullipotent stem cells is still compatible with a stem cell view of cancer initiation and progression. This review considers the origins of the cancer stem cell concept, and issues that need to be addressed to enhance its utility for developing methods for preventing and treating cancer.
1 citations
01 Jan 2011
TL;DR: Embryonic stem cells may acquire genetic and epigenetic changes upon prolonged passage in culture, which can confer on them more robust growth characteristics, potentially providing more robust cells for use in some applications.
Abstract: Embryonic stem (ES) cells may acquire genetic and epigenetic changes upon prolonged passage in culture, which can confer on them more robust growth characteristics. The genetic changes are often manifest cytogenetically as nonrandom gains of chromosomal regions that are also typically amplified in embryonal carcinoma (EC) cells, the malignant counterpart of ES cells. Although this raises some concerns for the future use of ES or induced pluripotent stem (iPS) cells in regenerative medicine, or in vitro screening applications, these concerns remain largely hypothetical. It may be that potential problems can be substantially mitigated when we understand more about the underlying causes and mechanisms of culture adaptation. At the same time, this phenomenon also provides a tool that can help dissect the mechanisms controlling stem cell behavior, while potentially providing more robust cells for use in some applications.