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Chotteau, VéroniqueORCID iD iconorcid.org/0000-0002-5370-4621
Alternative names
Publications (10 of 33) Show all publications
Hagrot, E., Oddsdóttir, H. Æ., Hosta, J. G., Jacobsen, E. W. & Chotteau, V. (2018). Retraction notice to “Poly-pathway model, a novel approach to simulate multiple metabolic states by reaction network-based model – Application to amino acid depletion in CHO cell culture” (Journal of Biotechnology (2016) 228 (37–39)(S0168165616301213)(10.1016/j.jbiotec.2016.03.015)). Journal of Biotechnology, 265
Open this publication in new window or tab >>Retraction notice to “Poly-pathway model, a novel approach to simulate multiple metabolic states by reaction network-based model – Application to amino acid depletion in CHO cell culture” (Journal of Biotechnology (2016) 228 (37–39)(S0168165616301213)(10.1016/j.jbiotec.2016.03.015))
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2018 (English)In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 265Article in journal (Refereed) Published
Abstract [en]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The authors of the paper wish to retract the paper due to the discovery of a calculation error in the processing of the raw data. The discovered error concerns the calculation of the specific uptake/secretion rates for several metabolites in one of the experimental conditions, i.e. glutamine omission (called Q0). In other words, in Figure 2, the variations of the metabolic fluxes for the condition Q0 are not correct. When this error is corrected, the resulting mathematical model changes (in particular for the results associated with Q0 conditions), several figures and tables are modified, and the interpretation of the fluxes in Q0 has to be slightly modified. Therefore the authors wish to retract the article. However, the error does not affect the modelling approach or the methodology presented in the article. Therefore, a revised version with the correct data has since been published: http://www.sciencedirect.com/science/article/pii/S0168165617302663. We apologize to the scientific community for the need to retract the article and the inconvenience caused.

Place, publisher, year, edition, pages
Elsevier B.V., 2018
Keywords
Erratum, retracted article
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-223179 (URN)10.1016/j.jbiotec.2017.11.013 (DOI)000418596500018 ()2-s2.0-85038872259 (Scopus ID)
Note

Export Date: 13 February 2018; Erratum; CODEN: JBITD. QC 20180228

Available from: 2018-02-28 Created: 2018-02-28 Last updated: 2018-02-28Bibliographically approved
Ravichandran, R., Åstrand, C., Patra, H. K., Turner, A. P. F., Chotteau, V. & Phopase, J. (2017). Intelligent ECM mimetic injectable scaffolds based on functional collagen building blocks for tissue engineering and biomedical applications. RSC Advances, 7(34), 21068-21078
Open this publication in new window or tab >>Intelligent ECM mimetic injectable scaffolds based on functional collagen building blocks for tissue engineering and biomedical applications
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2017 (English)In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 7, no 34, p. 21068-21078Article in journal (Refereed) Published
Abstract [en]

Hydrogels comprising natural extracellular matrix (ECM) components are very attractive as scaffolds for regenerative medicine applications due to their inherent biointeractive properties. Responsive materials that adapt to their surrounding environments and regulate transport of ions and bioactive molecules manifest significant advantages for biomedical applications. Although there are many exciting challenges, the opportunity to design, fabricate and engineer stimuli-responsive polymeric systems based on ECM components is particularly attractive for regenerative medicine. Here we describe a one-pot approach to fabricate in situ fast gellable intelligent ECM mimetic scaffolds, based on methacrylated collagen building blocks with mechanical properties that can be modulated in the kPa-MPa range and that are suitable for both soft and hard tissues. Physiochemical characterizations demonstrate their temperature and pH responsiveness, together with the structural and enzymatic resistance that make them suitable scaffolds for long-term use in regenerative medicine and biomedical applications. The multifunctionality of these hydrogels has been demonstrated as an in situ depot-forming delivery platform for the adjustable controlled release of proteins and small drug molecules under physiological conditions and as a structural support for adhesion, proliferation and metabolic activities of human cells. The results presented herein should be useful to the design and fabrication of tailor-made scaffolds with tunable properties that retain and exhibit sustained release of growth factors for promoting tissue regeneration.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2017
National Category
Other Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-207725 (URN)10.1039/c7ra02927f (DOI)000399722300040 ()2-s2.0-85018519019 (Scopus ID)
Note

QC 20170524

Available from: 2017-05-24 Created: 2017-05-24 Last updated: 2017-11-29Bibliographically approved
Al-Khalili, L., Gillner, K., Zhang, Y., Åstrand, C., Shokri, A., Hughes-Brittain, N., . . . Chotteau, V. (2016). Characterization of Human CD133+Cells in Biocompatible Poly(l-lactic acid) Electrospun Nano-Fiber Scaffolds. Journal of Biomaterials and Tissue Engineering, 6(12), 959-966
Open this publication in new window or tab >>Characterization of Human CD133+Cells in Biocompatible Poly(l-lactic acid) Electrospun Nano-Fiber Scaffolds
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2016 (English)In: Journal of Biomaterials and Tissue Engineering, ISSN 2157-9083, E-ISSN 2157-9091, Vol. 6, no 12, p. 959-966Article in journal (Refereed) Published
Abstract [en]

CD133+ cells are potential myogenic progenitors for skeletal muscle regeneration to treat muscular dystrophies. The proliferation of human CD133+ stem cells was studied for 14 days in 3D biomimetic electrospun poly-L-lactic acid (PLLA) nano-fiber scaffolds. Additionally, the myogenic differentiation of the cells was studied during the last 7 days of the culture period. The cells were homogeneously distributed in the 3D scaffolds while colony formation and myotube formation occurred in 2D. After a lag phase due to lower initial cell attachment and an adaptation period, the cell growth rate in 3D was comparable to 2D after 7 and 14 days of culture. The expression of the stem cell (SC) marker PAX7 was 1.5-fold higher in 3D than 2D while the differentiation markers MyoG, Desmin and MyoD were only slightly changed (or remain unchanged) in 3D but strongly increased in 2D (12.6, 3.9, and 7.9-fold), and the myotube formation observed in 2D was absent in 3D. The marker expression during proliferation and differentiation, together with the absence of myotubes in 3D, indicates a better maintenance of stemness in 3D PLLA and stronger tendency for spontaneous differentiation in 2D culture. This makes 3D PLLA a promising biomaterial for the expansion of functional CD133+ cells.

Place, publisher, year, edition, pages
American Scientific Publishers, 2016
Keywords
Myogenic Progenitor Cell, CD133+Cells, Myogenic Differentiation, 3D Cell Culturing, Electrospun Biodegradable Nano-Fiber Scaffold
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-198952 (URN)10.1166/jbt.2016.1531 (DOI)000387148500005 ()2-s2.0-84998636398 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme
Note

QC 20170113

Available from: 2017-01-13 Created: 2016-12-22 Last updated: 2017-11-29Bibliographically approved
Hagrot, E., Oddsdóttir, H. A., Hosta, J. G., Jacobsen, E. W. & Chotteau, V. (2016). Poly-pathway model, a novel approach to simulate multiple metabolic states by reaction network-based model - Application to amino acid depletion in CHO cell culture. Journal of Biotechnology, 228, 37-49
Open this publication in new window or tab >>Poly-pathway model, a novel approach to simulate multiple metabolic states by reaction network-based model - Application to amino acid depletion in CHO cell culture
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2016 (English)In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 228, p. 37-49Article in journal (Refereed) Published
Abstract [en]

Mammalian cell lines are characterized by a complex and flexible metabolism. A single model that could describe the variations in metabolic behavior triggered by variations in the culture conditions would be a precious tool in bioprocess development. In this paper, we introduce an approach to generate a poly-pathway model and use it to simulate diverse metabolic states triggered in response to removal, reduction or doubling of amino acids in the culture medium of an antibody-producing CHO cell line. Macro-reactions were obtained from a metabolic network via elementary flux mode enumeration and the fluxes were modeled by kinetic equations with saturation and inhibition effects from external medium components. Importantly, one set of kinetic parameters was estimated using experimental data of the multiple metabolic states. A good fit between the model and the data was obtained for the majority of the metabolites and the experimentally observed flux variations. We find that the poly-pathway modeling approach is promising for the simulation of multiple metabolic states.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Modeling, Metabolic flux analysis, Elementary flux modes, Chinese hamster ovary cells, Amino acid metabolism, Poly-pathway model
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-189659 (URN)10.1016/j.jbiotec.2016.03.015 (DOI)000377786500008 ()27060554 (PubMedID)2-s2.0-84973333168 (Scopus ID)
Funder
VINNOVA
Note

QC 20160718

Available from: 2016-07-18 Created: 2016-07-11 Last updated: 2017-11-28Bibliographically approved
Oddsdottir, H. A., Hagrot, E., Chotteau, V. & Forsgren, A. (2016). Robustness analysis of elementary flux modes generated by column generation. Mathematical Biosciences, 273, 45-56
Open this publication in new window or tab >>Robustness analysis of elementary flux modes generated by column generation
2016 (English)In: Mathematical Biosciences, ISSN 0025-5564, E-ISSN 1879-3134, Vol. 273, p. 45-56Article in journal (Refereed) Published
Abstract [en]

Elementary flux modes (EFMs) are vectors defined from a metabolic reaction network, giving the connections between substrates and products. EFMs-based metabolic flux analysis (MFA) estimates the flux over each EFM from external flux measurements through least-squares data fitting. The measurements used in the data fitting are subject to errors. A robust optimization problem includes information on errors and gives a way to examine the sensitivity of the solution of the EFMs-based MFA to these errors. In general, formulating a robust optimization problem may make the problem significantly harder. We show that in the case of the EFMs-based MFA, when the errors are only in measurements and bounded by an interval, the robust problem can be stated as a convex quadratic programming (QP) problem. We have previously shown how the data fitting problem may be solved in a column-generation framework. In this paper, we show how column generation may be applied also to the robust problem, thereby avoiding explicit enumeration of EFMs. Furthermore, the option to indicate intervals on metabolites that are not measured is introduced in this column generation framework. The robustness of the data is evaluated in a case-study, which indicates that the solutions of our non-robust problems are in fact near-optimal also when robustness is considered, implying that the errors in measurement do not have a large impact on the optimal solution. Furthermore, we showed that the addition of intervals on unmeasured metabolites resulted in a change in the optimal solution.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Metabolic network, Robust optimization, Least-squares, Elementary flux mode, Chinese hamster ovary cell
National Category
Bioinformatics (Computational Biology)
Identifiers
urn:nbn:se:kth:diva-184008 (URN)10.1016/j.mbs.2015.12.009 (DOI)000370908500004 ()26748294 (PubMedID)2-s2.0-84960376800 (Scopus ID)
Note

QC 20160330

Available from: 2016-03-30 Created: 2016-03-22 Last updated: 2018-01-10Bibliographically approved
Zhang, Y. & Chotteau, V. (2015). Observation of Chinese Hamster Ovary Cells retained inside the non-woven fiber matrix of the CellTank bioreactor. Data in Brief, 5, 586-588
Open this publication in new window or tab >>Observation of Chinese Hamster Ovary Cells retained inside the non-woven fiber matrix of the CellTank bioreactor
2015 (English)In: Data in Brief, ISSN 2352-3409, Vol. 5, p. 586-588Article in journal (Refereed) Published
Abstract [en]

This data article shows how the recombinant Chinese Hamster Ovary (CHO) cells are located in the interstices of the matrix fibers of a CellTank bioreactor after completion of a perfusion culture, supporting the article entitled "Very high cell density perfusion of CHO cells anchored in a non-woven matrix-based bioreactor" by Zhang et al. [1]. It provides a visualization of the cell distribution in the non-woven fiber matrix in a deeper view.

Place, publisher, year, edition, pages
Elsevier, 2015
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-181839 (URN)10.1016/j.dib.2015.10.006 (DOI)2-s2.0-84945243514 (Scopus ID)
Note

QC 20160211

Available from: 2016-02-11 Created: 2016-02-05 Last updated: 2018-01-10Bibliographically approved
Chotteau, V. (2015). Perfusion Processes. In: Mohamed Al-Rubeai (Ed.), Animal Cell Culture: (pp. 407-443). Switzerland Springer: Springer
Open this publication in new window or tab >>Perfusion Processes
2015 (English)In: Animal Cell Culture / [ed] Mohamed Al-Rubeai, Switzerland Springer: Springer , 2015, p. 407-443Chapter in book (Refereed)
Abstract [en]

The interest for perfusion is increasing nowadays. This new focus has emerged from a synergy of a demand for disposable equipment and the availability of robust cell separation device, as well as the need for higher flexibility and lower investment cost. The cell separation devices mostly used today are based on filtration, i.e. alternating flow filtration, tangential flow filtration, spin-filter, or acceleration/gravity, i.e. inclined settler, centrifuge, acoustic settler. This paper gives an introduction to the basic concepts of perfusion and its practical implementation. It reviews the actual cell separation devices and describes the approaches used in the field to develop and optimize the perfusion processes.

Place, publisher, year, edition, pages
Switzerland Springer: Springer, 2015
Series
Cell Engineering, ISSN 1389-6946
Keywords
perfusion, CHO, Chinese Hamster Ovary cells, mammalian cells, ATF, TFF, centritech, acoustic settler, inclined settler, perfusion rate
National Category
Bioprocess Technology
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-166112 (URN)10.1007/978-3-319-10320-4_13 (DOI)978-3-319-10320-4 (ISBN)
Note

QC 20150508

Available from: 2015-05-01 Created: 2015-05-01 Last updated: 2015-05-08Bibliographically approved
Zhang, Y., Stobbe, P., Silvander, C. O. & Chotteau, V. (2015). Very high cell density perfusion of CHO cells anchored in a non-woven matrix-based bioreactor. Journal of Biotechnology, 213, 28-41
Open this publication in new window or tab >>Very high cell density perfusion of CHO cells anchored in a non-woven matrix-based bioreactor
2015 (English)In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 213, p. 28-41Article in journal (Refereed) Published
Abstract [en]

Recombinant Chinese Hamster Ovary (CHO) cells producing IgG monoclonal antibody were cultivated in a novel perfusion culture system CellTank, integrating the bioreactor and the cell retention function. In this system, the cells were harbored in a non-woven polyester matrix perfused by the culture medium and immersed in a reservoir. Although adapted to suspension, the CHO cells stayed entrapped in the matrix. The cell-free medium was efficiently circulated from the reservoir into- and through the matrix by a centrifugal pump placed at the bottom of the bioreactor resulting in highly homogenous concentrations of the nutrients and metabolites in the whole system as confirmed by measurements from different sampling locations. A real-time biomass sensor using the dielectric properties of living cells was used to measure the cell density. The performances of the CellTank were studied in three perfusion runs. A very high cell density measured as 200 pF/cm (where 1 pF/cm is equivalent to 1 x 106 viable cells/mL) was achieved at a perfusion rate of 10 reactor volumes per day (RV/day) in the first run. In the second run, the effect of cell growth arrest by hypothermia at temperatures lowered gradually from 37 C to 29 C was studied during 13 days at cell densities above 100 pF/cm. Finally a production run was performed at high cell densities, where a temperature shift to 31 C was applied at cell density 100 pF/cm during a production period of 14 days in minimized feeding conditions. The IgG concentrations were comparable in the matrix and in the harvest line in all the runs, indicating no retention of the product of interest. The cell specific productivity was comparable or higher than in Erlenmeyer flask batch culture. During the production run, the final harvested IgG production was 35 times higher in the CellTank compared to a repeated batch culture in the same vessel volume during the same time period.

Place, publisher, year, edition, pages
[Zhang, Ye; Chotteau, Veronique] KTH, Royal Inst Technol, Cell Technol Grp CETEG, Sch Biotechnol,Dept Ind Biotechnol Bioproc Design, SE-10691 Stockholm, Sweden. [Stobbe, Per] PerfuseCell, DK-2840 Holte, Denmark. [Silvander, Christian Orrego] Belach Biotekn, SE-14250 Skogas, Sweden.: , 2015
Keywords
Disposable bioreactor, On-line biomass sensor, IgG production, Dielectric spectroscopy, Hypothermia
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:kth:diva-176326 (URN)10.1016/j.jbiotec.2015.07.006 (DOI)000362286400005 ()26211737 (PubMedID)2-s2.0-84942837005 (Scopus ID)
Note

QC 20151117

Available from: 2015-11-17 Created: 2015-11-03 Last updated: 2017-05-23Bibliographically approved
Oddsdóttir, H. Æ., Hagrot, E., Chotteau, V. & Forsgren, A. (2014). On dynamically generating relevant elementary flux modes in a metabolic network using optimization. Journal of Mathematical Biology
Open this publication in new window or tab >>On dynamically generating relevant elementary flux modes in a metabolic network using optimization
2014 (English)In: Journal of Mathematical Biology, ISSN 0303-6812, E-ISSN 1432-1416Article in journal (Refereed) Published
Abstract [en]

Elementary flux modes (EFMs) are pathways through a metabolic reaction network that connect external substrates to products. Using EFMs, a metabolic network can be transformed into its macroscopic counterpart, in which the internal metabolites have been eliminated and only external metabolites remain. In EFMs-based metabolic flux analysis (MFA) experimentally determined external fluxes are used to estimate the flux of each EFM. It is in general prohibitive to enumerate all EFMs for complex networks, since the number of EFMs increases rapidly with network complexity. In this work we present an optimization-based method that dynamically generates a subset of EFMs and solves the EFMs-based MFA problem simultaneously. The obtained subset contains EFMs that contribute to the optimal solution of the EFMs-based MFA problem. The usefulness of our method was examined in a case-study using data from a Chinese hamster ovary cell culture and two networks of varied complexity. It was demonstrated that the EFMs-based MFA problem could be solved at a low computational cost, even for the more complex network. Additionally, only a fraction of the total number of EFMs was needed to compute the optimal solution.

Keywords
Metabolic network, Optimization, Algorithm, Elementary flux mode, Metabolic flux analysis, Chinese hamster ovary cell
National Category
Mathematics
Research subject
Biotechnology; Mathematics
Identifiers
urn:nbn:se:kth:diva-165581 (URN)10.1007/s00285-014-0844-1 (DOI)000360851700006 ()2-s2.0-84941359801 (Scopus ID)
Funder
Swedish Research CouncilVINNOVA
Note

QC 20150518

Available from: 2015-04-29 Created: 2015-04-29 Last updated: 2017-12-04Bibliographically approved
Chotteau, V., Zhang, Y. & Clincke, M.-F. (2014). Very High Cell Density in Perfusion of CHO Cells by ATF, TFF, Wave Bioreactor, and/or CellTank Technologies: Impact of Cell Density and Applications. In: Ganapathy Subramanian (Ed.), Continuous Processing in Pharmaceutical Manufacturing: (pp. 339-356). Germany Weinheim: Wiley-VCH Verlagsgesellschaft
Open this publication in new window or tab >>Very High Cell Density in Perfusion of CHO Cells by ATF, TFF, Wave Bioreactor, and/or CellTank Technologies: Impact of Cell Density and Applications
2014 (English)In: Continuous Processing in Pharmaceutical Manufacturing / [ed] Ganapathy Subramanian, Germany Weinheim: Wiley-VCH Verlagsgesellschaft, 2014, p. 339-356Chapter in book (Other academic)
Place, publisher, year, edition, pages
Germany Weinheim: Wiley-VCH Verlagsgesellschaft, 2014
Keywords
CellTank, perfusion, filtration, ultra filtration, Chinese hamster ovary (CHO) cell, high-cell density perfusion processes, monoclonal antibody, ATF, TFF
National Category
Bioprocess Technology
Identifiers
urn:nbn:se:kth:diva-166113 (URN)10.1002/9783527673681.ch13 (DOI)2-s2.0-84949057950 (Scopus ID)9783527673681 (ISBN)
Note

QC 20150508

Available from: 2015-05-01 Created: 2015-05-01 Last updated: 2015-05-08Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5370-4621

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