Evercyte GmbH

Vienna, Austria

Evercyte GmbH

Vienna, Austria
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Dellago H.,University of Natural Resources and Life Sciences, Vienna | Preschitz-Kammerhofer B.,University of Natural Resources and Life Sciences, Vienna | Terlecki-Zaniewicz L.,University of Natural Resources and Life Sciences, Vienna | Schreiner C.,University of Natural Resources and Life Sciences, Vienna | And 16 more authors.
Aging Cell | Year: 2013

Cellular senescence of normal human cells has by now far exceeded its initial role as a model system for aging research. Many reports show the accumulation of senescent cells in vivo, their effect on their microenvironment and its double-edged role as tumour suppressor and promoter. Importantly, removal of senescent cells delays the onset of age-associated diseases in mouse model systems. To characterize the role of miRNAs in cellular senescence of endothelial cells, we performed miRNA arrays from HUVECs of five different donors. Twelve miRNAs, comprising hsa-miR-23a, hsa-miR-23b, hsa-miR-24, hsa-miR-27a, hsa-miR-29a, hsa-miR-31, hsa-miR-100, hsa-miR-193a, hsa-miR-221, hsa-miR-222 and hsa-let-7i are consistently up-regulated in replicatively senescent cells. Surprisingly, also miR-21 was found up-regulated by replicative and stress-induced senescence, despite being described as oncogenic. Transfection of early passage endothelial cells with miR-21 resulted in lower angiogenesis, and less cell proliferation mirrored by up-regulation of p21CIP1 and down-regulation of CDK2. These two cell-cycle regulators are indirectly regulated by miR-21 via its validated direct targets NFIB (Nuclear factor 1 B-type), a transcriptional inhibitor of p21CIP1, and CDC25A, which regulates CDK2 activity by dephosphorylation. Knock-down of either NFIB or CDC25A shows a phenocopy of over-expressing miR-21 in regard to cell-cycle arrest. Finally, miR-21 over-epxression reduces the replicative lifespan, while stable knock-down by sponges extends the replicative lifespan of endothelial cells. Therefore, we propose that miR-21 is the first miRNA that upon its knock-down extends the replicative lifespan of normal human cells. © 2013 John Wiley & Sons Ltd and the Anatomical Society.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.86M | Year: 2017

All chemicals whether they are drugs, cosmetics, agrochemicals or others need to be tested for their safety to man and the environment. The use of whole animal studies for the prediction of adverse effects in man, is problematic due to species dependent effects, high costs and a large burden to animals in terms of numbers and suffering. While there have been major improvements in human in vitro and in silico techniques, there is still a lack of an integrated risk assessment platform. The in3 proposal aims to significantly further the development of animal-free chemical and nanomaterial (NM) safety evaluation by creating a scientific and training program aimed at integrating human in vitro testing with computational approaches. The project will focus on human induced pluripotent stem cells (hiPSC) derived tissues, including liver, kidney, brain, lung and vasculature and to utilise mechanistic toxicology, quantitative adverse outcome pathways, biokinetics, cheminformatics and modelling approaches to derive testable prediction models. hiPSC present the major advantages provide non-cancerous derived tissues with identical genetic backgrounds. All Early Stage Researchers (ESRs) will work towards the same goal, utilising the same chemicals, donor cells, assays and software packages. All data will be centrally housed in standardised formats, appropriately annotated and linked with protocols and material information. While ESRs will hone their skills in their own field of expertise, they will also collaborate to create an in depth safety evaluation testing platform for the chosen test compounds. By interaction, problem solving, training and secondments over the three years, they will acquire a unique set of interdisciplinary skills for chemical and NM safety assessment. The project aims to accelerate the realisation of animal-free safety assessment and to graduate 15 PhD students with the ideal skill sets to carry out the strategy designed in in3 in the near future.


The forecasted increase in the number of older people for this century will be accompanied by an increase of those with disabilities. Disability is usually preceded by a condition named frailty that encompasses changes associated with ageing, life styles and chronic diseases. To detect and intervene on it is of outstanding importance to prevent disability, as recovery from disability is unlikely. Recent documents stress the necessity of testing the clinical utility (in terms of risk prediction, diagnosis validity and prognostic significance) of the existing definition of frailty by using combinations of clinical criteria (current definition) and lab Biomarkers (BMs). We will measure the levels of blood and urine omic-based BMs in old people selected from eight cohorts, which include up to 75,000 participants, using standardized and innovative technology (WP1). This figure will allow us to test the research questions with a high power and validity. Combining these lab BMs with clinical BMs, we will develop predictive, diagnostic and prognostic models (WP2), with its modulation by nutrition and physical activity, in general old population and in old people showing some characteristics that confer a high risk for developing frailty (selected cardiovascular risk factors and diseases) (WP4). After that, a selected set of BMs will be validated prospectively (WP3) and assessed to find the best-fitted models (WP4). These models will guide the development of the ready-to-use kits to be implemented in the clinical settings. These kits will be at the center of dissemination and exploitation activities (WP5, WP6). A well-balanced consortium distributed over the individual tasks in the respective work packages will carry it out, with a strong participation of SMEs. In summary, FRAILOMIC is original, relevant, pertinent, feasible, overcome the usual research bottlenecks on Biomarkers, and fits perfectly with the topics addressed by the HEALTH.2012.2.1.1-2 call in human subjects


Hackl M.,TAmiRNA GmbH | Heilmeier U.,University of California at San Francisco | Weilner S.,Evercyte GmbH | Grillari J.,Evercyte GmbH | Grillari J.,University of Natural Resources and Life Sciences, Vienna
Molecular and Cellular Endocrinology | Year: 2016

Biomarkers are essential tools in clinical research and practice. Useful biomarkers must combine good measurability, validated association with biological processes or outcomes, and should support clinical decision making if used in clinical practice. Several types of validated biomarkers have been reported in the context of bone diseases. However, because these biomarkers face certain limitations there is an interest in the identification of novel biomarkers for bone diseases, specifically in those that are tightly linked to the disease pathology leading to increased fracture-risk. MicroRNAs (miRNAs) are the most abundant RNA species to be found in cell-free blood. Encapsulated within microvesicles or bound to proteins, circulating miRNAs are remarkably stable analytes that can be measured using gold-standard technologies such as quantitative polymerase-chain-reaction (qPCR). Nevertheless, the analysis of circulating miRNAs faces several pre-analytical as well as analytical challenges. From a biological view, there is accumulating evidence that miRNAs play essential roles in the regulation of various biological processes including bone homeostasis. Moreover, specific changes in miRNA transcription levels or miRNA secretory levels have been linked to the development and progression of certain bone diseases. Only recently, results from circulating miRNAs analysis in patients with osteopenia, osteoporosis and fragility fractures have been reported. By comparing these findings to studies on circulating miRNAs in cellular senescence and aging or muscle physiology and sarcopenia, several overlaps were observed. This suggests that signatures observed during osteoporosis might not be specific to the pathophysiology in bone, but rather integrate information from several tissue types. Despite these promising first data, more work remains to be done until circulating miRNAs can serve as established and robust diagnostic tools for bone diseases in clinical research, clinical routine and in personalized medicine. © 2015 The Authors


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.1.1-1 | Award Amount: 15.78M | Year: 2013

The aim of SYBIL is to carry out extensive functional validation of the genetic determinants of rare and common skeletal diseases and the age related factors contributing to these painful conditions. To achieve this goal SYBIL will gather complementary translational and transnational scientists, systems biologists, disease modellers, leading SMEs and industrialists that will perform in-depth characterisation (complete molecular phenotyping) of pre-clinical models (cellular and animal) for a variety of common and rare skeletal diseases. SYBIL will establish a systematic pipeline of in vitro, ex vivo and in vivo models of increasing complexity and will also make use of novel technologies such as iPS cells and exclusive Virtual Patient software to identify potential therapeutic targets for further validation through simultaneous modelling of fundamental and complex physiological pathways. SYBIL will rely on i) an Omics Knowledge Factory for systematically generating new knowledge on skeletal disease pathophysiology and to generate the relevant Omics profiles necessary to detect and validate new disease determinants, biomarkers and therapeutic targets for future clinical developments, and ii) a Systems Biology Hub to integrate the high-throughput and data-dense information, to gain a global understanding of pathophysiological commonalities between different skeletal diseases and recognize predominant shared pathways and mechanisms that may represent new targeted routes to treatment. SYBIL will also identify potential modifier genes and study the epigenome that will ultimately influence the timing and efficacy of new personalised treatments. Overall SYBIL achievements will tremendously boost the efficient pre-clinical assessment and development of therapeutics against skeletal diseases and thus indirectly reduce their social and healthcare burden.


PubMed | Evercyte GmbH, TAmiRNA GmbH, University of California at San Francisco and University of Natural Resources and Life Sciences, Vienna
Type: | Journal: Molecular and cellular endocrinology | Year: 2016

Biomarkers are essential tools in clinical research and practice. Useful biomarkers must combine good measurability, validated association with biological processes or outcomes, and should support clinical decision making if used in clinical practice. Several types of validated biomarkers have been reported in the context of bone diseases. However, because these biomarkers face certain limitations there is an interest in the identification of novel biomarkers for bone diseases, specifically in those that are tightly linked to the disease pathology leading to increased fracture-risk. MicroRNAs (miRNAs) are the most abundant RNA species to be found in cell-free blood. Encapsulated within microvesicles or bound to proteins, circulating miRNAs are remarkably stable analytes that can be measured using gold-standard technologies such as quantitative polymerase-chain-reaction (qPCR). Nevertheless, the analysis of circulating miRNAs faces several pre-analytical as well as analytical challenges. From a biological view, there is accumulating evidence that miRNAs play essential roles in the regulation of various biological processes including bone homeostasis. Moreover, specific changes in miRNA transcription levels or miRNA secretory levels have been linked to the development and progression of certain bone diseases. Only recently, results from circulating miRNAs analysis in patients with osteopenia, osteoporosis and fragility fractures have been reported. By comparing these findings to studies on circulating miRNAs in cellular senescence and aging or muscle physiology and sarcopenia, several overlaps were observed. This suggests that signatures observed during osteoporosis might not be specific to the pathophysiology in bone, but rather integrate information from several tissue types. Despite these promising first data, more work remains to be done until circulating miRNAs can serve as established and robust diagnostic tools for bone diseases in clinical research, clinical routine and in personalized medicine.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP-2008-4.0-1 | Award Amount: 7.39M | Year: 2009

We propose a multidisciplinary program, focusing on the development of novel approaches for directing the differentiation, proliferation and tissue-tropism of specific hematopoietic lineages, using micro- and nano-fabricated cell chips. We will use advanced nanofabricated surfaces functionalized with specific biomolecules, and microfluidics cell chips to specify and expend regulatory immune cells for treating diverse inflammatory and autoimmune disorders in an organ- and antigen-specific manner. The proposed cell-chip will create ex-vivo microenvironments mimicking in-vivo cell-cell interactions and molecular signals involved in differentiation and proliferation of hematopoietic cells. Cell chip development and optimization will be supported by high throughput microscopy to select for optimal conditions. Educated cells will be employed for in vivo experiments in mice and the methodology will be further adapted for human cell populations, and applied for clinical diagnosis and therapy as well as the developments of clinically-relevant devices. Regulatory T-cells are extremely promising cells for treatment of inflammatory and auto-immune disease, as well as for tolerance induction in organ transplantation. To be effective they must be produced conveniently, at large numbers with an optimally tuned phenotype. The methodology is suggested to overcome current obstacles in obtaining therapeutically significant numbers of T cells. We propose to apply the suggested methodology for treating different inflammatory or autoimmune diseases including type-1 diabetes using targeted immunotherapeutic approaches. Developing new methods for producing large numbers of finely-tuned and tissue-targeted regulatory cells will make this approach clinically viable. This novel methodology can be extended to directing differentiation of other specific T-cell and hematopoietic lineages, with possible applications for targeting other autoimmune diseases and treating tumors or graft rejection.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: NMP-2008-2.3-1 | Award Amount: 5.26M | Year: 2010

Cell therapy and tissue engineering are emerging as novel therapeutic paradigms for myocardial repair. The rationale behind the cell replacement approach is based on the assumption that an increase in the number of functional cardiomyocytes within the diseased area may improve the mechanical properties of this compromised region. A common strategy attempts to initially combine, ex-vivo, cells with polymeric scaffolds to generate a construct, followed by in-vivo engraftment onto the heart muscle. Despite first encouraging results, the clinical utility of these approaches is hampered by the paucity of cell sources for human cardiomyocytes and by the limited direct functional integration of grafted cells and high degree of donor cell death following cell grafting in host myocardial tissue. NanoCARD will create a conceptually new type of biomimetic nanoscopically designed scaffold able to generate cardiac tissue replacement for the myocardium. Within our project we will design novel cellular environments with broad but precisely-controlled diversity in chemical composition, physical properties, and geometrical spacing of individual peptides on the nanometre scale. The capability of these environments to regulate cell response will be explored by high throughput approaches using a new chip technology developed within the project. An additional unique concept for controlling the function of cardiac cells is given by applying periodic mechanical strain in the range of heart frequency during the tissue engineering process. The knowledge gained within NanoCARD will be translated into the design and production of a novel biocompatible nanostructured device (therapeutic surface) with a desired bioactivity inducing specific behaviour of endothelial cells and cardiomyocytes to revolutionise treatment of myocardial defects. The inclusion of relevant companies in the consortium assures the identification of opportunities for the intended product developments.


Weilner S.,University of Natural Resources and Life Sciences, Vienna | Weilner S.,Evercyte GmbH | Grillari-Voglauer R.,University of Natural Resources and Life Sciences, Vienna | Grillari-Voglauer R.,Evercyte GmbH | And 6 more authors.
Acta Orthopaedica | Year: 2015

Background and purpose - We reviewed the current state of research on microRNAs in age-related diseases in cartilage and bone. Methods - PubMed searches were conducted using separate terms to retrieve articles on (1) the role of microRNAs on aging and tissue degeneration, (2) specific microRNAs that influence cellular and organism senescence, (3) microRNAs in age-related musculoskeletal conditions, and (4) the diagnostic and therapeutic potential of microRNAs in age-related musculoskeletal conditions. Results - An increasing number of studies have identified microRNAs associated with cellular aging and tissue degeneration. Specifically in regard to frailty, microRNAs have been found to influence the onset and course of age-related musculoskeletal conditions such as osteoporosis, osteoarthritis, and posttraumatic arthritis. Both intracellular and extracellular microRNAs may be suitable to function as diagnostic biomarkers. Interpretation - The research data currently available suggest that microRNAs play an important role in orchestrating age-related processes and conditions of the musculoskeletal system. Further research may help to improve our understanding of the complexity of these processes at the cellular and extracellular level. The option to develop microRNA biomarkers and novel therapeutic agents for the degenerating diseases of bone and cartilage appears to be promising. © 2015, Informa Healthcare. All rights reserved.


Weilner S.,University of Natural Resources and Life Sciences, Vienna | Weilner S.,Ludwig Boltzmann Institute for Clinical and Experimental Traumatology | Schraml E.,University of Natural Resources and Life Sciences, Vienna | Redl H.,Ludwig Boltzmann Institute for Clinical and Experimental Traumatology | And 4 more authors.
Experimental Gerontology | Year: 2013

Changes of factors circulating in the systemic environment during human aging have been investigated for a long time. Only recently however, miRNAs have been found to be secreted into the systemic and tissue environments where they are protected from RNAses by either carrier proteins or by being packaged into microvesicles. These miRNAs are then taken up by recipient cells, changing the cellular behavior by the classical miRNA induced silencing of target mRNAs. The origin of circulating miRNAs, however, is in most instances unclear, but senescent cells emerge as a possible source of such secreted miRNAs. Since differences in the circulating miRNAs have been found in a variety of age-associated diseases, and accumulation of senescent cells in the elderly emerges as a possible detrimental factor in aging, it is well conceivable that these miRNAs might contribute to the functional decline observed during aging of organisms.Therefore, we here give an overview on current knowledge on microvesicular secretion of miRNAs, changes of the systemic and tissue environments during aging of cells and organisms. Finally, we summarize current knowledge on miRNAs that are found to be specific for age-associated diseases. © 2012 Elsevier Inc.

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