| 1. |
- J T Carrondo, Manuel J T, et al.
(författare)
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How can measurement, monitoring, modeling and control advance cell culture in industrial biotechnology?
- 2012
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Ingår i: Biotechnology Journal. - : Wiley-VCH Verlag Berlin. - 1860-6768 .- 1860-7314. ; 7:12, s. 1522-1529
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Tidskriftsartikel (refereegranskat)abstract
- This report highlights the potential of measurement, monitoring, modeling and control ((MC)-C-3) methodologies in animal and human cell culture technology. In particular, state-of-the-art of (MC)-C-3 technologies and their industrial relevance of existing technology are addressed. It is a summary of an expert panel discussion between biotechnologists and biochemical engineers with both academic and industrial backgrounds. The latest ascents in (MC)-C-3 are discussed from a cell culture perspective for industrial process development and production needs. The report concludes with a set of recommendations for targeting (MC)-C-3 research toward the industrial interests. These include issues of importance for biotherapeutics production, miniaturization of measurement techniques and modeling methods.
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| 2. |
- Kreij, Karl, 1975-, et al.
(författare)
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On-line detection of microbial contaminations in animal cell reactor cultures using an electronic nose device
- 2005
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Ingår i: Cytotechnology (Dordrecht). - : Springer Science and Business Media LLC. - 0920-9069 .- 1573-0778. ; 48:1-3, s. 41-58
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Tidskriftsartikel (refereegranskat)abstract
- An electronic nose (EN) device was used to detect microbial and viral contaminations in a variety of animal cell culture systems. The emission of volatile components from the cultures accumulated in the bioreactor headspace, was sampled and subsequently analysed by the EN device. The EN, which was equipped with an array of 17 chemical gas sensors of varying selectivity towards the sampled volatile molecules, generated response patterns of up to 85 computed signals. Each 15 or 20 min a new gas sample was taken generating a new response pattern. A software evaluation tool visualised the data mainly by using principal component analysis. The EN was first used to detect microbial contaminations in a Chinese hamster ovary (CHO) cell line producing a recombinant human macrophage colony stimulating factor (rhM-CSF). The CHO cell culture was contaminated by Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida utilis which all were detected. The response patterns from the CHO cell culture were compared with monoculture references of the microorganisms. Second, contaminations were studied in an Sf-9 insect cell culture producing another recombinant protein (VP2 protein). Contaminants were detected from E. coli, a filamentous fungus and a baculovirus. Third, contamination of a human cell line, HEK-293, infected with E. coli exhibited comparable results. Fourth, bacterial contaminations could also be detected in cultures of a MLV vector producer cell line. Based on the overall experiences in this study it is concluded that the EN method has in a number of cases the potential to be developed into a useful on-line contamination alarm in order to support safety and economical operation for industrial cultivation. © Springer 2005.
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| 3. |
- Mandenius, Carl-Fredrik, et al.
(författare)
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Toward Preclinical Predictive Drug Testing for Metabolism and Hepatotoxicity by Using In Vitro Models Derived from Human Embryonic Stem Cells and Human Cell Lines - A Report on the Vitrocellomics EU-project
- 2011
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Ingår i: ATLA-ALTERNATIVES TO LABORATORY ANIMALS. - : Fund for Replacement of Animals in Medical Experiments; 1999. - 0261-1929 .- 2632-3559. ; 39:2, s. 147-171
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Tidskriftsartikel (refereegranskat)abstract
- Drug-induced liver injury is a common reason for drug attrition in late clinical phases, and even for post-launch withdrawals. As a consequence, there is a broad consensus in the pharmaceutical industry, and within regulatory authorities, that a significant improvement of the current in vitro test methodologies for accurate assessment and prediction of such adverse effects is needed. For this purpose, appropriate in vivo-like hepatic in vitro models are necessary, in addition to novel sources of human hepatocytes. In this report, we describe recent and ongoing research toward the use of human embryonic stem cell (hESC)-derived hepatic cells, in conjunction with new and improved test methods, for evaluating drug metabolism and hepatotoxicity. Recent progress on the directed differentiation of human embryonic stem cells to the functional hepatic phenotype is reported, as well as the development and adaptation of bioreactors and toxicity assay technologies for the testing of hepatic cells. The aim of achieving a testing platform for metabolism and hepatotoxicity assessment, based on hESC-derived hepatic cells, has advanced markedly in the last 2-3 years. However, great challenges still remain, before such new test systems could be routinely used by the industry. In particular, we give an overview of results from the Vitrocellomics project (EU Framework 6) and discuss these in relation to the current state-of-the-art and the remaining difficulties, with suggestions on how to proceed before such in vitro systems can be implemented in industrial discovery and development settings and in regulatory acceptance.
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| 4. |
- Roldao, Antonio, 1979, et al.
(författare)
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Viruses and virus-like particles in biotechnology: Fundamentals and applications
- 2019
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Ingår i: Comprehensive Biotechnology. ; , s. 633-656
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Although viruses are simple biological systems, they are capable of evolving highly efficient techniques for infecting cells, expressing their genomes, and generating new copies of themselves. It is possible to genetically manipulate most of the different classes of known viruses in order to produce recombinant viruses that express foreign proteins. Recombinant viruses have been used in gene therapy to deliver selected genes into higher organisms, in vaccinology and immunotherapy, and as important research tools to study the structure and function of these proteins. Virus-like particles (VLPs) are multiprotein structures that mimic the organization and conformation of authentic native viruses but lack the viral genome. They have been applied not only as prophylactic and therapeutic vaccines but also as vehicles in drug and gene delivery and, more recently, as tools in nanobiotechnology. In this chapter, basic and advanced features of viruses and VLPs are presented and their major applications are discussed. The different production platforms based on animal cell technology are explained, and their main challenges and future perspectives are explored. The implications of large-scale production of viruses and VLPs are discussed in the context of process control, monitoring, and optimization. The main upstream and downstream technical challenges are identified and discussed accordingly.
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