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Relevant bibliographies by topics / Bioreactors; Cell culture; Large scale

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Academic literature on the topic 'Bioreactors; Cell culture; Large scale'

Author: Grafiati

Published: 4 June 2021

Last updated: 6 February 2022

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Journal articles on the topic "Bioreactors; Cell culture; Large scale"

1

Grün, Christoph, Brigitte Altmann, and Eric Gottwald. "Advanced 3D Cell Culture Techniques in Micro-Bioreactors, Part I: A Systematic Analysis of the Literature Published between 2000 and 2020." Processes 8, no. 12 (December 15, 2020): 1656. http://dx.doi.org/10.3390/pr8121656.

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Bioreactors have proven useful for a vast amount of applications. Besides classical large-scale bioreactors and fermenters for prokaryotic and eukaryotic organisms, micro-bioreactors, as specialized bioreactor systems, have become an invaluable tool for mammalian 3D cell cultures. In this systematic review we analyze the literature in the field of eukaryotic 3D cell culture in micro-bioreactors within the last 20 years. For this, we define complexity levels with regard to the cellular 3D microenvironment concerning cell–matrix-contact, cell–cell-contact and the number of different cell types present at the same time. Moreover, we examine the data with regard to the micro-bioreactor design including mode of cell stimulation/nutrient supply and materials used for the micro-bioreactors, the corresponding 3D cell culture techniques and the related cellular microenvironment, the cell types and in vitro models used. As a data source we used the National Library of Medicine and analyzed the studies published from 2000 to 2020.

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Xing, Zizhuo, Brian M. Kenty, Zheng Jian Li, and Steven S. Lee. "Scale-up analysis for a CHO cell culture process in large-scale bioreactors." Biotechnology and Bioengineering 103, no. 4 (July 1, 2009): 733–46. http://dx.doi.org/10.1002/bit.22287.

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Allen, Leah M., John Matyas, Mark Ungrin, David A. Hart, and Arindom Sen. "Serum-Free Culture of Human Mesenchymal Stem Cell Aggregates in Suspension Bioreactors for Tissue Engineering Applications." Stem Cells International 2019 (November 7, 2019): 1–18. http://dx.doi.org/10.1155/2019/4607461.

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Mesenchymal stem cells (MSCs) have the capacity to differentiate towards bone, fat, and cartilage lineages. The most widely used culture and differentiation protocols for MSCs are currently limited by their use of serum-containing media and small-scale static culture vessels. Suspension bioreactors have multiple advantages over static culture vessels (e.g., scalability, control, and mechanical forces). This study sought to compare the formation and culture of 3D aggregates of human synovial fluid MSCs within suspension bioreactors and static microwell plates. It also sought to elucidate the benefits of these techniques in terms of productivity, cell number, and ability to generate aggregates containing extracellular matrix deposition. MSCs in serum-free medium were either (1) inoculated as single cells into suspension bioreactors, (2) aggregated using static microwell plates prior to being inoculated in the bioreactor environment, or (3) aggregated using microwell plates and kept in the static environment. Preformed aggregates that were size-controlled at inoculation had a greater tendency to form large, irregular super aggregates after a few days of suspension culture. The single MSCs inoculated into suspension bioreactors formed a more uniform population of smaller aggregates after a definite culture period of 8 days. Both techniques showed initial deposition of extracellular matrix within the aggregates. When the relationship between aggregate size and ECM deposition was investigated in static culture, midsized aggregates (100-300 cells/aggregate) were found to most consistently maximize sGAG and collagen productivity. Thus, this study presents a 3D tissue culture method, which avoids the clinical drawbacks of serum-containing medium that can easily be scaled for tissue culture applications.

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Koller, MR, SG Emerson, and BO Palsson. "Large-scale expansion of human stem and progenitor cells from bone marrow mononuclear cells in continuous perfusion cultures." Blood 82, no. 2 (July 15, 1993): 378–84. http://dx.doi.org/10.1182/blood.v82.2.378.378.

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Abstract There is a growing consensus that clinical practice in the areas of bone marrow (BM) transplantation and gene therapy will rely on the ex vivo expansion of hematopoietic cells. We report here on the development of continuously perfused culture systems (bioreactor systems) that expand human stem and progenitor cells from BM mononuclear cell (MNC) populations obtained without cell enrichment. In three separate experiments, 10 bioreactors were each inoculated with 3 x 10(7) BM MNC from patients undergoing marrow harvest for autologous transplantation. At various times thereafter (between days 6 and 16), duplicate bioreactors were harvested and cells were analyzed. The bioreactors contained three cell populations that were analyzed separately: nonadherent cells; cells that were loosely adherent to the endogenously formed stromal layer; and an adherent cell layer that required trypsinization for removal. Total cell numbers increased continuously to give an overall 10-fold (range, 8- to 11-fold) expansion by day 14. The adherent stromal layer significantly expanded to more than 2 x 10(7) cells, but remained less than 6% of the total cell population. Colony-forming unit-granulocyte-macrophage (CFU-GM) numbers expanded 21-fold (range, 12- to 34-fold) by day 14 and, because this expansion was greater than that for total cells, CFU-GM were enriched by as much as fourfold by day 14. Burst-forming unit-erythroid (BFU-E) numbers peaked earlier than did CFU-GM numbers, with a 12-fold (range, 6- to 18-fold) expansion obtained on day 8. In contrast to CFU- GM, which were predominantly nonadherent, BFU-E were more evenly distributed between the three cell populations. Stem cell activity was measured by the long-term culture-initiating cell (LTC-IC) limiting dilution assay. The number of LTC-IC per reactor consistently increased with time in all cultures, resulting in a 7.5-fold (range, 3.4- to 9.8- fold) expansion. In summary, more than 3 billion cells, containing 12 million CFU-GM, were reproducibly generated from the equivalent of a 10 to 15 ml BM aspirate. These data indicate that small numbers of BM MNC can be readily expanded ex vivo in continuous perfusion cultures, and that such ex vivo expansion may have direct applications in clinical and experimental BM transplantation.

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Koller, MR, SG Emerson, and BO Palsson. "Large-scale expansion of human stem and progenitor cells from bone marrow mononuclear cells in continuous perfusion cultures." Blood 82, no. 2 (July 15, 1993): 378–84. http://dx.doi.org/10.1182/blood.v82.2.378.bloodjournal822378.

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There is a growing consensus that clinical practice in the areas of bone marrow (BM) transplantation and gene therapy will rely on the ex vivo expansion of hematopoietic cells. We report here on the development of continuously perfused culture systems (bioreactor systems) that expand human stem and progenitor cells from BM mononuclear cell (MNC) populations obtained without cell enrichment. In three separate experiments, 10 bioreactors were each inoculated with 3 x 10(7) BM MNC from patients undergoing marrow harvest for autologous transplantation. At various times thereafter (between days 6 and 16), duplicate bioreactors were harvested and cells were analyzed. The bioreactors contained three cell populations that were analyzed separately: nonadherent cells; cells that were loosely adherent to the endogenously formed stromal layer; and an adherent cell layer that required trypsinization for removal. Total cell numbers increased continuously to give an overall 10-fold (range, 8- to 11-fold) expansion by day 14. The adherent stromal layer significantly expanded to more than 2 x 10(7) cells, but remained less than 6% of the total cell population. Colony-forming unit-granulocyte-macrophage (CFU-GM) numbers expanded 21-fold (range, 12- to 34-fold) by day 14 and, because this expansion was greater than that for total cells, CFU-GM were enriched by as much as fourfold by day 14. Burst-forming unit-erythroid (BFU-E) numbers peaked earlier than did CFU-GM numbers, with a 12-fold (range, 6- to 18-fold) expansion obtained on day 8. In contrast to CFU- GM, which were predominantly nonadherent, BFU-E were more evenly distributed between the three cell populations. Stem cell activity was measured by the long-term culture-initiating cell (LTC-IC) limiting dilution assay. The number of LTC-IC per reactor consistently increased with time in all cultures, resulting in a 7.5-fold (range, 3.4- to 9.8- fold) expansion. In summary, more than 3 billion cells, containing 12 million CFU-GM, were reproducibly generated from the equivalent of a 10 to 15 ml BM aspirate. These data indicate that small numbers of BM MNC can be readily expanded ex vivo in continuous perfusion cultures, and that such ex vivo expansion may have direct applications in clinical and experimental BM transplantation.

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Claessen, Maria, Eszter Varga, Steven Heshusius, Esther Heideveld, Martin Hansen, Anna Visser, Marijke Thiel-Valkhof, et al. "Large Scale Culture and Differentiation of Erythroblasts from PBMC and iPSC." Blood 132, Supplement 1 (November 29, 2018): 2319. http://dx.doi.org/10.1182/blood-2018-99-118882.

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Abstract Transfusion of donor-derived red blood cells to aleviate anemia is the most common form of cellular therapy. In addition, red blood cells hold great promise as delivery agents of e.g. specific drugs or enzymes. However, the source depends on donor availability and carries a potential risk of alloimmunization and blood borne diseases. More than 30 bloodgroup systems encode >300 bloodgroup antigens and bloodgroup matching becomes increasingly challenging in a multiethnic society. Particularly the chronically transfused patients are at risk for alloimmunisation. In vitro cultured, customizable red blood cells (cRBC) would negate these concerns and introduce precision medicine both in transfusion medicine as well as in drug delivery applications. We aim to produce human cRBC at large-scale and cost effective, for which we need to optimize culture conditions and reduce cost-drivers. We adapted our protocols to GMP culture requirements, which reproducibly provided pure human erythroid cultures within 25 days with a 3.4x107 times expansion from peripheral blood mononuclear cells without prior CD34+ isolation. This expansion depended on the serum free medium we produce, which is supplemented with erythropoietin (Epo, 1 U/ml), stem cell factor (SCF) and glucocorticoids. Expanded erythroblasts CD71 highCD235low/- were differentiated for 10 days in medium supplemented with 5% human plasma, heparin and a higher concentration of Epo (10U/ml) yielding CD71dimCD235a+CD44+CD117-DRAQ5- cRBC. More than 90% of the cells enucleated and expressed adult hemoglobin as well as the correct blood group antigens. Passaging cRBC through a leukodepletion filter yielded 100% enucleated, stable cRBC. Deformability was measured by an Automated Rheoscope and Cell Analyser (ARCA), and oxygen equilibrium curves were measured with a Hemox analyzer. Both parameters were similar in cRBC and freshly isolated reticulocytes. RNA sequencing was performed daily during differentiation and revealed expression dynamics of important erythroid processes, e.g. increased expression of genes involved in blood group expression, globin regulation, and erythroid specific metabolic enzymes, concommittant with loss of expression of genes involved in the formation of organelles, and cell proliferation. The culture process is compatible with upscaling using 5L G-Rex bioreactors., Currently we are preparing a clinical study using biotinylated cRBC. Ultimately, however, large scale production requires an immortal source, for which we aim to use human induced pluripotent stem cells (iPSC) established from rare donors that lack most blood group antigens. Using single cell passaging of iPSC and differentiation in colonies, we generate at average 2x105 cRBC per single iPSC. However, the cRBC cultured from iPSC were less stable following enucleation, and expressed embryonic type globins. Comparison of transcriptome data from iPSC-derived erythroid cells at distinct differentiation stages with erythroid cells at similar stages that were cultured from adult- or cord blood mononuclear cells, or from fetal liver confirmed that most iPSC-derived erythroid cells largely express an embryonic RNA profile. In conclusion, our current protocols enable us to test cRBC cultured from adult peripheral blood for their stability after transfusion. Concurrently, we develop novel bioreactors to upscale the production, and we optimise the protocol to generate cRBC from immortal iPSC lines with near 'universal donor' genotypes. Disclosures No relevant conflicts of interest to declare.

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Gerlach, J. C., K. Klöppel, C. MÜller, N. Schnoy, M. D. Smith, and P. Neuhaus. "Hepatocyte Aggregate Culture Technique for Bioreactors in Hybrid Liver Support Systems." International Journal of Artificial Organs 16, no. 12 (December 1993): 843–46. http://dx.doi.org/10.1177/039139889301601210.

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Utilizing a modified culture technique for hepatocytes, a high performance suspension culture is possible in which hepatocytes spontaneously form cell aggregates. The aggregates of 20-100 cells have been histologically confirmed to hold a three-dimensional structure, they show a long-term external metabolism and a survival time comparable with standard adhesion cultures. This technique has several advantages in the construction of large scale bioreactors for hybrid liver support systems.

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Chen, Keda, Chaonan Li, Ying Wang, Zhenwei Shen, Yikai Guo, Xiaoping Li, and Yanjun Zhang. "Optimization of Vero Cells Grown on a Polymer Fiber Carrier in a Disposable Bioreactor for Inactivated Coxsackievirus A16 Vaccine Development." Vaccines 9, no. 6 (June 7, 2021): 613. http://dx.doi.org/10.3390/vaccines9060613.

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At present, there are no vaccines available for hand, foot, and mouth disease, which is caused by Coxsackie virus A16 (CVA16) infection. In the present study, we isolated epidemic strains of CVA16 and optimized the production of the virus in Vero cells. The system comprised growing the infected cells on polymer fiber paper carriers in a serum-free medium containing 0.5% (w/v) lactalbumin hydrolysate a mini bioreactor. Disposable Bioflo310 and AmProtein Current perfusion bioreactors were used to monitor virus infection and Vero cell culture. The total number of cells increased from 1.5 × 109 to 3.0 × 1010. In our optimized culture process, the virus titer reached 7.8 × 107 TCID50/mL at three days after infection. The inactivated CVA16 prepared from our optimized culture procedure elicited a slightly higher neutralizing antibody titer compared with that derived from routine culture procedures. These results will promote the large-scale production of inactivated CVA16 vaccines using nonwoven polymer fiber paper cell cultures.

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Eghbali, Hadis, Michele M. Nava, Gabriella Leonardi, Davod Mohebbi-Kalhori, Roberto Sebastiano, Abdolreza Samimi, and Manuela T. Raimondi. "An Experimental-Numerical Investigation on the Effects of Macroporous Scaffold Geometry on Cell Culture Parameters." International Journal of Artificial Organs 40, no. 4 (April 2017): 185–95. http://dx.doi.org/10.5301/ijao.5000554.

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Introduction Perfused bioreactors have been demonstrated to be effective in the delivery of nutrients and in the removal of waste products to and from the interior of cell-populated three-dimensional scaffolds. In this paper, a perfused bioreactor hosting a macroporous scaffold provided with a channel is used to investigate transport phenomena and culture parameters on cell growth. Methods MG63 human osteosarcoma cells were seeded on macroporous poly(ε-caprolactone) scaffolds provided with a channel. The scaffolds were cultured in a perfused bioreactor and in static conditions for 5 days. Cell viability and growth were assessed while the concentration of oxygen, glucose and lactate were measured. An in silico, multiphysics, numerical model was set up to study the fluid dynamics and the mass transport of the nutrients in the perfused bioreactor hosting different scaffold geometries. Results The experimental and numerical results indicated that the specific cell metabolic activity in scaffolds cultured under perfusion was 30% greater than scaffolds cultured under static conditions. In addition, the scaffold provided with a channel enabled the shear stress to be controlled, the initial seeding density to be retained, and adequate mass transport and waste removal. Conclusions We show that the macroporous scaffold provided with a channel cultured in a macroscale bioreactor can be a robust reference experimental model system to systematically investigate and assess crucial culture parameters. We also show that such an experimental model system can be employed as a simplified “representative unit” to improve the performance of both perfused culture systems and hollow, fiber-integrated scaffolds for large-scale tissue engineering.

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DEAN, ROBERT C., SABHASH B. KARKARE, NITYA G. RAY, PETER W. RUNSTADLER, and K. VENKATASUBRAMANIAN. "Large-Scale Culture of Hybridoma and Mammalian Cells in Fluidized Bed Bioreactors." Annals of the New York Academy of Sciences 506, no. 1 Biochemical E (November 1987): 129–46. http://dx.doi.org/10.1111/j.1749-6632.1987.tb23815.x.

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Dissertations / Theses on the topic "Bioreactors; Cell culture; Large scale"

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Mardikar, Sudhanshu H. "Shear damage to animal cells due to disengagement of spherical cap bubbles." Thesis, University of Reading, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242331.

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Scott, W. H. "The effect of potential large-scale bioreactor environmental heterogeneities during fed-batch culture on the performance of an industrially-relevant GS-CHO cell culture, producing an IgG antibody." Thesis, University of Birmingham, 2011. http://etheses.bham.ac.uk//id/eprint/2820/.

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This study aimed to study the effect of potential large-scale bioreactor environmental heterogeneities during fed-batch culture on the performance of an industrially-relevant GS-CHO cell culture, producing an IgG antibody. Heterogeneity was created by a two-compartment scale-down model, using a well-mixed stirred tank reactor (STR) and plug flow reactor (PFR). A peristaltic pump was used to continuously circulate cell culture from the STR through the PFR. Standard culture parameters were measured and flow cytometry was used to indicate cell viability and mode of cell death. The results essentially fell into two categories: those without circulation and those with it. In all cases with recirculation, whether nutrients and alkali were added into the STR or the PFR, significantly decreased culture duration (\(\sim\)48 hours shorter) and antibody titre (\(\sim\)20% decrease) were found compared to those experiments without circulation. It was impossible to conclude anything concerning the impact of bioreactor heterogeneities. Nevertheless, damage associated with peristaltic pumping has relevance to the many aspects of cell culture processes that require transfer of cells in suspension. The 'squeezing' motion of peristaltic pumps may impose sufficient mechanical stress to have decreased cell culture performance. The high biocompatibility of the materials used suggests long-term incompatibility is less likely.

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Zhang, Xiaowei. "Orbitally shaken bioreactors for mammalian cell culture : engineering characterization and bioprocess scale-up /." [S.l.] : [s.n.], 2009. http://library.epfl.ch/theses/?nr=4492.

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Barrett, T. A. "Microwell evaluation of mammalian cell lines for large scale culture." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1444162/.

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Experimentation in shaken microplate formats offers a potential platform technology for the evaluation and optimisation of cell culture conditions. Provided that the results obtained are reliable, and indicative of large scale performance, it should be possible to obtain process design data early and cost effectively. This work describes a detailed engineering characterisation of liquid mixing and gas-liquid mass transfer in microwell systems and their impact on suspension cell cultures. Furthermore, an initial attempt at scaling a microwell culture to shake flasks and a 5-L stirred-tarik reactor is made. For suspension cultures of murine hybridoma cells producing IgGl, 24-well plates have been characterised in terms of power dissipation (P/V) (via CFD). Fluid flow patterns and oxygen transfer rate as a function of shaking frequency and liquid fill volume. Predicted ka values varied between 1.3 and 29 h_1 mixing time, quantified using decolourisation of iodine, varied from 1.7 s to 3.5 h while the P/V ranged from 5 to 35 W m-3. CFD simulations of the shear rate predicted hydrodynamic forces will not be lethal to cells. High shaking speed (> 250 rpm) was shown to be detrimental to cell growth, while a combination of low shaking speed and high well fill volume (120 rpm. 2000 //l) resulted in oxygen limited conditions. Using matched average energy dissipation as a basis for scale translation, cell growth and antibody titre were found to be similar in a 24-well plate. 250 ml shake flask and 5-L stirred-tank reactor. Overall this work has demonstrated that cell culture performed in shaken microwell plates can provide data that is both reproducible and representative of larger-scale cultures. Linked with automation this provides a route towards the high throughput evaluation of robust cell lines under realistic process conditions.

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Sani, M. H. B. "Evaluation of microwell based systems and miniature bioreactors for rapid cell culture bioprocess development and scale-up." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1473531/.

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The increased use of antibodies for human therapy has driven rational approaches to accelerate bioprocess development in producing cost effective and highly productive antibodies. The potential of microwell based systems and miniature bioreactors (MBR) to mimic the scalability and operations of conventional bench reactors are seen as an alternative. This study has investigated the microtitre plate (MTP), microMatrix and MBR (HEL-BioXplore) as scale-down mimic for rapid and accurate reproduction of Chinese hamster ovary (CHO) cell growth and product yields in bench scale stirred tank reactors. A microtitre plate with sandwich lid CR1524a (for slow growing animal cells) was found to be suitable for CHO cell cultivation. An evaluation of feeding approaches in MTP showed that bolus addition resulted in 9.19 x 106 cell mL-1 and 38 % higher IgG titres compared to addition of FeedBeads. In order to enable scale translation, the engineering parameters for the MBR were characterised with regard to mixing time, volumetric oxygen transfer coefficient and power input. The MBR system was fitted with either direct driven impeller or magnetically driven impeller with singular hole impeller or horseshoe sparger. The combination of the direct driven impeller and horseshoe type sparger with bolus addition was selected as the best configuration and produced 8.89 x 106 cell mL-1 and 0.84 gL-1 IgG titres. Additionally, a prototype micro-Matrix system was characterised for its performance in a cell culture process. The micro-Matrix with controlled aeration and continuous feeding supported a cell concentration of 8.67 x 106 cell mL-1 and viability >90 % after 264 hours. Furthermore, scale translations of the studied systems were evaluated at the matched mixing time of 6 s with conventional lab scale 5L stirred tank reactors (STR). The scale-up studies demonstrated that the miniature systems were able to mimic the performance of the conventional bench reactors. Results from the scale-up studies between the MTP, MBR and STR with bolus feeding addition showed a comparable viable cell concentration of 9.30 x 106 cell mL-1 , 9.56 x 106 cell mL-1 and 10.04 x 106 cell mL-1 and IgG titres of 0.92, 0.69 and 0.83 gL-1 respectively. Whereas, scale translation studies between micro-Matrix and MBR with continuous feeding gave equivalent viable cell concentration with 11.1 x 106 cell mL-1 and 9.76 x 106 cell mL-1 and IgG titres of 0.50 gL-1 and 0.64 gL-1 respectively. Overall, the miniature bioreactors evaluated have the potential for cell screening and optimisation studies which could generate early data for bioprocess development.

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Konagaya, Shuhei. "Design of cell culture substrates for large-scale preparation of neural cells." 京都大学 (Kyoto University), 2013. http://hdl.handle.net/2433/174963.

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Puschmann, E. "Liquidus tracking : a promising vitrification technique for large scale encapsulated 3-D cell culture preservation." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1469902/.

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Liver organ shortage is an increasing problem worldwide and many die each year waiting for a new liver. In case of acute liver failure a bioartificial liver (BAL) device could “buy” time until a donor liver is available or until the liver has spontaneously undergone self-repair. For the clinical application of a BAL large quantities of cells should be available immediately necessitating cryo-banking. However, cryopreservation of large volumes results in increased ice formation and increased cell death. Ice formation can be prevented by vitrification, but the high cryoprotectant agent (CPA) concentrations needed are normally toxic to mammalian cells. Short exposure time minimizes toxicity but can only be achieved in small samples where fast cooling rates can be reached. To reduce CPA toxicity a vitrification machine (Liquidus Tracker) designed by Planer plc was used, which provides the lowest toxic effect that can be established for a given CPA concentration by decreasing the sample temperature to just above the melting point of that particular mix. The CPA concentration is then gradually increased as temperature is decreased along the liquidus curve. The first aspect of this thesis was to standardise a rapid and reliable method to describe post-stress viability. A digital imaging system was used to evaluate membrane integrity and enzyme activity by quantifying the fluorescence signal of fluorescein and propidium iodide. To understand the Liquidus Tracking (LT) process but also to pre-test conditions for automatic LT, different methods to carry out manual LT were established, evaluated and improved. To further increase cell viability a low-toxicity CPA solution was developed with the requirement of low viscosity so that it may be used within the Liquidus Tracker. Finally improvements were applied to automatic Liquidus Tracking. The development of a new stirring system substantially increased post-warming viability. In conclusion, an optimised large scale slow cooling vitrification protocol was developed for alginate encapsulated liver cells which may be used in a BAL.

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Books on the topic "Bioreactors; Cell culture; Large scale"

1

K, Lydersen Bjorn, ed. Large scale cell culture technology. Munich: Hanser Publishers, 1987.

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Joseph, Feder, and Tolbert William R, eds. Large-scale mammalian cell culture. San Diego: Academic P., 1985.

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Large-scale Mammalian Cell Culture. Elsevier, 1985. http://dx.doi.org/10.1016/b978-0-12-250430-3.x5001-6.

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Lydersen, Bjorn K. Large Scale Cell Culture Technology. Wiley-Interscience, 1993.

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Joseph, Feder, Tolbert William R, and American Chemical Society. Division of Microbial and Biochemical Technology., eds. Large-scale mammalian cell culture. Orlando: Academic Press, 1985.

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BjornK, Lydersen, ed. Large scale cell culture technology. Chichester: Carl Hanser Verlag, 1987.

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1946-, Lubiniecki Anthony S., ed. Large-scale mammalian cell culture technology. New York: Dekker, 1990.

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Large Scale Cell Culture Technology (Hanser Publishers). Oxford University Press, USA, 1986.

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Alfred, Doig, ed. Protein therapeutics production : large-scale mammalian cell culture. Westborough, MA: DMD Publications, 2005.

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Gao, Jianwei. Genetic stability and large-scale cultivation of genetically modified tobacco cells. 1990.

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Book chapters on the topic "Bioreactors; Cell culture; Large scale"

1

Yinliang, Chen, Dong Shupei, Gu Xiaohua, Yan Chun, Song Jiali, Chen Liesheng, and Chen Wenlan. "Large-Scale Culture of Vero Cells on GT-2 Microcarrier in Cell Culture Bioreactors." In Biochemical Engineering for 2001, 347–49. Tokyo: Springer Japan, 1992. http://dx.doi.org/10.1007/978-4-431-68180-9_92.

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Hashimoto, T., and S. Azechi. "Bioreactors for the Large-Scale Culture of Plant Cells." In Biotechnology in Agriculture and Forestry, 104–22. Berlin, Heidelberg: Springer Berlin Heidelberg, 1988. http://dx.doi.org/10.1007/978-3-642-73026-9_4.

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Sakai, Y., and M. Suzuki. "A Hollow Fiber Bioreactor Immobilizing Hepatocyte Spheroids Rapidly Formed by Large-Scale Suspension Culture." In Animal Cell Technology: Basic & Applied Aspects, 417–21. Dordrecht: Springer Netherlands, 1994. http://dx.doi.org/10.1007/978-94-011-0848-5_63.

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Mitsuhashi, Jun. "Large-Scale Cell Culture." In Invertebrate Tissue Culture Methods, 387–400. Tokyo: Springer Japan, 2002. http://dx.doi.org/10.1007/978-4-431-67875-5_42.

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Tramper, J., J. M. Vlak, and C. D. de Gooijer. "Scale up aspects of sparged insect-cell bioreactors." In Insect Cell Culture: Fundamental and Applied Aspects, 221–29. Dordrecht: Springer Netherlands, 1996. http://dx.doi.org/10.1007/0-306-46850-6_19.

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Steinhäuser, Dirk. "Case Study Large Scale Cell Culture Facility." In Cells and Culture, 619–20. Dordrecht: Springer Netherlands, 2010. http://dx.doi.org/10.1007/978-90-481-3419-9_105.

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Kim, Wan-Seop. "Cell Culture Bioreactors: Controls, Measurements, and Scale-Down Model." In Manual of Industrial Microbiology and Biotechnology, 676–84. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555816827.ch48.

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Ozturk, Sadettin S. "Equipment for Large-Scale Mammalian Cell Culture." In Mammalian Cell Cultures for Biologics Manufacturing, 69–92. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/10_2013_259.

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Schorn, P., H. Voigt, and W. Noé. "Device for Cell Culture Fluid Sampling from Lab Scale Bioreactors." In Animal Cell Technology: Developments Towards the 21st Century, 1123–25. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-011-0437-1_176.

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Ozturk, S. S. "Optimization and Scale-Up of High Density Cell Culture Bioreactors." In Advances in Bioprocess Engineering, 133–39. Dordrecht: Springer Netherlands, 1994. http://dx.doi.org/10.1007/978-94-017-0641-4_19.

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Conference papers on the topic "Bioreactors; Cell culture; Large scale"

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Rasponi, Marco, Francesco Piraino, Nicola Cagol, Matteo Moretti, Gianfranco B. Fiore, and Alberto Redaelli. "Development of a Microfluidic Device Embedding High-Conductivity Flexible Electrodes for Three-Dimensional Cell Culture Stimulations." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80658.

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Successful treatment of cardiovascular diseases has so far been limited by the lack of suitable autologous tissue to restore injured tissues. Currently, a novel encouraging frontier for such treatment is represented by tissue engineering [1]. Although traditional bioreactors for cardiac tissue engineering, based on a classical macro-scale approach, are widely used, research for identifying effective stimulation patterns has not lead to robust results yet. In this sense, the phenomena driving cell growth and differentiation become more addressable in reduced-scale systems, and microfluidics represents a valid alternative approach to overcome traditional bioreactors limitations. In order to favor the differentiation paths, recently developed microfluidic bioreactors tend to increase the control within cell culture chambers by coupling mechanical, electrical, thermical or optical effects. In particular, stem cell differentiation into cardiomyocytes seems to draw beneficial effects from electrical and mechanical stimulations [2]. This work introduces a simple method of embedding conductive and flexible material within microfluidic devices as a means to realize microscale bioreactors for cell electro-mechanical stimulation. Thanks to the proposed technology, high conductivity three-dimensional (3D) electrodes can be simply realized.

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Liovic, Petar, Ilija D. Šutalo, Laurence Meagher, and George O. Lovrecz. "Computations of Flow Environments in Medium-Scale Stirred-Tank Bioreactors for Stem Cell Expansion." In ASME 2014 4th Joint US-European Fluids Engineering Division Summer Meeting collocated with the ASME 2014 12th International Conference on Nanochannels, Microchannels, and Minichannels. American Society of Mechanical Engineers, 2014. http://dx.doi.org/10.1115/fedsm2014-21967.

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The flow in a New Brunswick Scientific (NBS (now Eppendorf)) 5 L stirred-tank bioreactor (STR) partially filled with 2.2 L of water and agitated at 60 rpm using a pitched-blade impeller is studied in this work, to determine the suitability of the configuration for expanding stem cell lines. Computational Fluid Dynamics (CFD) model development and testing in this work has found Large Eddy Simulation (LES) to be essential for model fidelity and for capturing spatiotemporal stress fluctuations. Stresses were at levels similar to or even higher than those known to damage stem cells or modulate their cellular function to favour differentiation instead of phenotype maintenance. The results raise questions as to the appropriateness of such STRs for stem cell expansion, and motivate better experimental studies to properly quantify the spatiotemporal variability in fluid shear stresses and its effect on stem cell expansion and stem cell fate.

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Zhu, Tingting, Hao Zhang, Yiran Guo, Bifeng Liu, and Peng Fei. "A Wireless-and-Lensless Microscope for In-Situ, High-resolution Imaging of Ultra-large-scale Cell Culture." In Asia Communications and Photonics Conference. Washington, D.C.: OSA, 2016. http://dx.doi.org/10.1364/acpc.2016.af4k.3.

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Marshall, Lauren, Andra Frost, Tim Fee, and Joel Berry. "Assembly and Characterization of 3D, Vascularized Breast Cancer Tissue Mimics." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14199.

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Drug development platforms such as two-dimensional (2D) in vitro cell culture systems and in vivo animal studies do not accurately predict human in vivo effectiveness of candidate therapeutics [1]. Cell culture systems have limited similarities to primary human cells and tissues as only one cell type is employed and animal studies have a generally limited ability to recapitulate human drug response as different species have differences in metabolism, physiology, and behavior. Mike Leavitt, a former U.S. Secretary of Health and Human Services, has stated that “currently, nine out of ten experimental drugs fail in clinical studies because we cannot accurately predict how they will behave in people based on laboratory and animal studies” [2]. Therefore, this research project is focused on developing an in vitro platform to test candidate therapeutics for more efficacious predictions of human response. We have fabricated a three-dimensional (3D) breast cancer tissue volume containing a vascular network. This vascular network is necessary because current in vitro systems (e.g., rotating bioreactors, suspension of spheroids, and growth on a porous scaffold) are limited in size (1–2 mm) by their absence of micrometer-scale blood flow micro-channels that allow for oxygen and nutrient diffusion into the tissue [4]. The extracellular matrix scaffold has been developed to mimic the native extracellular matrix and includes relevant cell types (e.g., human breast cancer epithelial cells and human breast fibroblasts) along with the prefabricated vascular network (prevascularization). These systems are intended to support long-term growth, recapitulate physiological tissue function, and accurately model response to treatment. It is hypothesized that the development of reproducible tissue volumes will transform breast cancer drug development by providing reliable, cost-effective models that can more accurately predict therapeutic efficacy than current preclinical in vivo and in vitro models.

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Huang, Alice H., Nuzhat A. Motlekar, Ashley Stein, Eileen M. Shore, Scott L. Diamond, and Robert L. Mauck. "High-Throughput Screening of Chemical Libraries for Modulators of Mesenchymal Stem Cell Chondrogenesis." In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-193118.

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Mesenchymal stem cells (MSCs) are a multi-potential cell type that can be induced to differentiate to a variety of tissue-specific cell phenotypes, including cartilage (chondrogenesis) and bone (osteogenesis). Given this multi-potentiality, MSCs are a promising cell source for exploring developmental paradigms and for tissue engineering (TE) applications. For cartilage formation assays, MSCs are collected in high-density pellets and treated with specific biofactors, including TGF-β superfamily members and dexamethasone in a chemically defined medium (CM) [1]. During chondrogenesis, extracellular matrix (ECM) rich in glycosaminoglycan (GAG) and type II collagen is synthesized. While MSC chondrogenesis is well-characterized using existing protocols, the effect of alternative biofactors, their doses and combinations requires laborious combinatorial studies [2]. High-throughput screening (HTS) overcomes this limitation through the simultaneous layout and query of a large number of conditions within a single plate. HTS depends on the use of precise robotic liquid handling systems and on the development of sensitive, validated, and readily quantifiable assays. In a recent study, we optimized cell culture and assay procedures for HTS by minimizing cell number, handling and culture duration [3]. We successfully reduced the time scale from 21 to 7 days and the number of cells required from 225K to 30K cells per pellet. Further, we developed a novel in-well digestion protocol to enable high-throughput analysis and minimize handling. In this study, we have further streamlined these assays for HTS by providing a rapid and robotic approach for layout, culture, and analysis of ECM deposition using ‘micro’ MSC pellets (10K cells per pellet) in a 384-well format. Furthermore, we have carried out an initial screen of the NINDS small molecule library and demonstrated the feasibility of this technology for use in HTS of chondrogenesis.

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Gong, Haibo, Antonios Kontsos, Yoontae Kim, Peter I. Lelkes, Qingwei Zhang, Donggang Yao, Kavan Hazeli, and Jack G. Zhou. "Micro Characterization of Mg and Mg Alloy for Biodegradable Orthopedic Implants Application." In ASME 2012 International Manufacturing Science and Engineering Conference collocated with the 40th North American Manufacturing Research Conference and in participation with the International Conference on Tribology Materials and Processing. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/msec2012-7395.

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Magnesium as a candidate metallic biomaterial for biodegradable orthopedic implants was evaluated in-vitro in terms of degradation behavior, biocompatibility and mechanical property both in macro- and micro-scale. Micro structure of pure Mg and AZ61 after degradation in both simulated body fluid (SBF) and cell culture environment were analyzed. Different from AZ61, pure Mg degraded at a higher rate and attracted large amount of salt precipitation which formed a layer covering the surface. Much less pitting degradation and salt deposition were observed on both pure Mg and AZ61 in cell culture environment compared to in SBF. After culturing for 7 days, EAhy926 cells growing on AZ61 showed significant higher proliferation rate as of cells growing on pure Mg. Higher proliferation rates indicated that cells grew better on slow-degrading AZ61 than on fast-degrading pure Mg. Cells growing on AZ61 proliferated much better and assembled together to form a consistent tissue-like micro-structure, while cells spread and reached out on the surface of pure Mg, possibly due to low cell density and lack of cellular communication. The elastic modulus and tensile yield strength of magnesium are closer to those of natural bone than other commonly used metallic biomaterials. It was shown that Mg was biodegradable, biocompatible and had appropriate mechanical strength, thus Mg and its alloys showed great potential for deployment in a new generation of biodegradable orthopedic implants.

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Tung, Yen-Ting, and Gou-Jen Wang. "In Vitro Development of Microvessels Using a Scaffold of Cylindrical PLGA." In ASME 2016 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2016. http://dx.doi.org/10.1115/detc2016-59550.

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The microvascular network is a simple but critical system that is responsible for various important biological mechanisms in the bodies of all animals. The ability to generate a functional microvessel in vitro not only makes it possible to engineer vital tissue of considerable size but also serves as a platform for biomedical studies. In this study, we propose a simple method for fabricating customized cylinder micro-scaffolds for the in vitro development of microvascular networks. By integrating micro-electro-mechanical systems techniques with thermal reflow, we design and fabricate a micro-scale hemi-cylinder photoresist template. Then, a replica mold of polydimethylsiloxane, produced by casting, is used to generate microvascular network scaffolds of poly(lactide-co-glycolide) (PLGA). We selected the human umbilical vein endothelial cell (HUVEC) as our model endothelial cell, seeded it onto both sides of the PLGA scaffold, and cultured it using a traditional approach with no pumping system. Results from fluorescent staining demonstrate that the scaffold was covered with HUVECs and that the desired microvascular network and pattern was generated in vitro. The proposed method enables the culture of cells on a scaffold using a conventional culture approach and allows continuous monitoring of cell conditions. The cell-covered scaffold can serve as a framework for building large tissues, while the formed microvascular network, after degradation of the biodegradable PLGA cylinder, can be used as the core of a vascular chip for in vitro circulation studies.

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Vehar, G. A. "THE PRESENT STATE OF GENE TECHNOLOGY IN THE MANUFACTURE OF HUMAN COAGULATION PROTEINS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644755.

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The production of pharmaceuticals from human plasma that are useful in the treatment of bleeding disorders had its beginning with the development of the Cohn fractionation procedure in the 1940's. As a result of these advances, concentrates became available for the treatment of the hemophilias. Although of low purity and subject to contamination by hepatitis virus, the availability of these compounds resulted in dramatic improvements in the life expectancy and quality of life of afflicted individuals. The numerous problems associated with production of pharmaceuticals from pooled plasma made these products obvious goals for recombinant DNA technology as soon as the commercial aspects of the field became apparent. The subsequent contamination of blood products with the AIDS virus has resulted in an urgent need for a production source that is independent of human plasma. Several industrial and academic laboratories have cloned the cDNA's for human factors VIII and IX. In addition to these proteins, the utility of factor Vila in the treatment of hemophiliacs with inhibitors has shown promise. Efforts to develop a recombinant preparation of factor Vila are at a comparable stage of development as factors VIII and IX. Continuing efforts have resulted in the successful expression of these recombinant proteins in mammalian cell lines, thereby successfully completing the first steps of commercial development.Although much interest has focused upon the theoretical superiority of recombinant proteins as therapeutics, one must keep in mind that there are numerous developmental aspects of large-scale production and regulatory issues that must be addressed and solved before these drugs will be available. The coagulation proteins are complex glycoproteins that will in all probability require mammalian cell cell culture in order to produce functional proteins. The fact that these preparations will be administered over the lifetime of the patient serves to reinforce that the recombinant products be as similar to the natural proteins as possible, further supporting the concept of mammalian cell expression systems.Regulatory approval of a recombinant product are fundamentally no different than those for any other product in regards to efficacy, potency, purity, and identity. There are, however, additional considerations that must be addressed in the production of recombinant cell culture derived biologies. These relate to the possible presence in the final product of pathogenic and tumorigenic agents, and possible contamination by cell culture and cell substrate compounds. A detailed characterization of the production cell line will therefore be required, including identification and characterization of any associated viral particles. These cells must be capable of being reproducibly grown, while maintaining protein production, on ascale (tens of thousands of liters) suitable to meet the market demand of the specific protein. Apurification process must be established capable of handling the resulting large volumes of feedstock, generating a protein preparation of high purity (greater than 99% pure). Numerous assays must be developed to quantitate the purity and identity of the resulting recombinant pharmaceutical on a lot by lot basis.Studies to date have shown that recombinant forms of factors VIII and IX, produced by laboratory processes, are very similar to the plasma-derived forms as assessed by a variety of in vitro and in vivo tests. Although these results are promising, the ultimate safety and efficacy testing of these drugs will have to await the initiation of human clinical trials. Such studies will have to await the successful completion of the certain regulatory concerns. Clinical trials should begin within the near future, hopefully leading to a source of these products independent of pooled human plasma.

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