{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T01:53:03Z","timestamp":1788400383577,"version":"build-2803163510"},"reference-count":80,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2021-127933OB-C21"],"award-info":[{"award-number":["PID2021-127933OB-C21"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["DIN2020-011559"],"award-info":[{"award-number":["DIN2020-011559"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Catedra Bionet","award":["2020-2024"],"award-info":[{"award-number":["2020-2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Plant cell cultures offer a promising platform for producing valuable biomolecules, yet their use in bioreactors remains under-optimized. Compared to animal or microbial cells, plant cells grow more slowly, limiting productivity. A common bioprocess strategy to improve yields involves controlling dissolved oxygen (DO) levels. However, little research has focused on combining agitation and aeration to regulate oxygen in plant cell cultures within bioreactors. The aim of this study was to evaluate the impact of an oxygen cascade mixing agitation and aeration on plant cell growth in stirred-tank systems. By maintaining 30% DO through this approach, the specific growth rate (\u00b5) increased from 0.082 d\u22121 to 0.144 d\u22121 on average in Nicotiana benthamiana cultures at the 2 L scale, decreasing batch lengths from 21 to 10 days. These conditions were successfully replicated in a 7 L stainless-steel pilot bioreactor using previous values of geometry, kLa and NRE as scale-up criteria, obtaining a \u00b5 of 0.161 d\u22121. These results demonstrate that plant cell cultures\u2019 efficiency can be enhanced by using standard bioprocess parameters. While this work confirms the feasibility of cascade oxygen control for improvements in growth, further studies are needed to evaluate its specific impact on biomolecule production across different systems.<\/jats:p>","DOI":"10.3390\/plants14182879","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T14:31:41Z","timestamp":1758033101000},"page":"2879","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cascade Oxygen Control Enhances Growth of Nicotiana benthamiana Cell Cultures in Stirred-Tank Bioreactors"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3222-1943","authenticated-orcid":false,"given":"Fuensanta","family":"Verd\u00fa-Navarro","sequence":"first","affiliation":[{"name":"Bioprocess Pilot Plant, Bionet, 30320 Fuente \u00c1lamo, Spain"},{"name":"Instituto de Biotecnolog\u00eda Vegetal, Universidad Polit\u00e9cnica de Cartagena, 30202 Cartagena, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-3296","authenticated-orcid":false,"given":"Juan Antonio","family":"Moreno-Cid","sequence":"additional","affiliation":[{"name":"Bioprocess Pilot Plant, Bionet, 30320 Fuente \u00c1lamo, Spain"},{"name":"Probelte SAU, 30500 Molina de Segura, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2432-2613","authenticated-orcid":false,"given":"Julia","family":"Weiss","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnolog\u00eda Vegetal, Universidad Polit\u00e9cnica de Cartagena, 30202 Cartagena, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4693-9948","authenticated-orcid":false,"given":"Marcos","family":"Egea-Cortines","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnolog\u00eda Vegetal, Universidad Polit\u00e9cnica de Cartagena, 30202 Cartagena, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.copbio.2009.04.004","article-title":"Closed Photo-Bioreactors as Tools for Biofuel Production","volume":"20","author":"Lehr","year":"2009","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1002\/elsc.201400203","article-title":"Biopolymers Made from Methane in Bioreactors","volume":"15","author":"Chidambarampadmavathy","year":"2015","journal-title":"Eng. Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"132401","DOI":"10.1016\/j.chemosphere.2021.132401","article-title":"Exploring the Potential of Slaughterhouse Waste Valorization: Development and Scale-up of a New Bioprocess for Medium-Chain Length Polyhydroxyalkanoates Production","volume":"287","author":"Acedos","year":"2022","journal-title":"Chemosphere"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fang, Z., Lyu, J., Li, J., Li, C., Zhang, Y., Guo, Y., Wang, Y., Zhang, Y., and Chen, K. (2022). Application of Bioreactor Technology for Cell Culture-Based Viral Vaccine Production: Present Status and Future Prospects. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.921755"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"C580","DOI":"10.1152\/ajpcell.00408.2022","article-title":"Advancing Our Understanding of Bioreactors for Industrial-Sized Cell Culture: Health Care and Cellular Agriculture Implications","volume":"325","author":"Ge","year":"2023","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Verd\u00fa-Navarro, F., Moreno-Cid, J.A., Weiss, J., and Egea-Cortines, M. (2023). The Advent of Plant Cells in Bioreactors. Front. Plant Sci., 14.","DOI":"10.3389\/fpls.2023.1310405"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s00299-021-02693-6","article-title":"Cellular Engineering of Plant Cells for Improved Therapeutic Protein Production","volume":"40","author":"Karki","year":"2021","journal-title":"Plant Cell Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104161","DOI":"10.1016\/j.arabjc.2022.104161","article-title":"Plant Cell Culture Technologies: A Promising Alternatives to Produce High-Value Secondary Metabolites","volume":"15","author":"Abdulhafiz","year":"2022","journal-title":"Arab. J. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11816-023-00821-0","article-title":"Plant-Made Pharmaceuticals: Exploring Studies for the Production of Recombinant Protein in Plants and Assessing Challenges Ahead","volume":"17","author":"Lee","year":"2023","journal-title":"Plant Biotechnol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1089\/scd.2023.0135","article-title":"Applications of Plant-Made Fibroblast Growth Factor for Human Pluripotent Stem Cells","volume":"33","author":"Jia","year":"2024","journal-title":"Stem Cells Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1211\/jpp.61.11.0001","article-title":"Antimalarial Compounds Isolated from Plants Used in Traditional Medicine","volume":"61","author":"Bero","year":"2009","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10546","DOI":"10.1021\/jf302809k","article-title":"Anti-Inflammatory Procyanidins and Triterpenes in 109 Apple Varieties","volume":"60","author":"Andre","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1039\/c2np20060k","article-title":"Ursane-Type Pentacyclic Triterpenoids as Useful Platforms to Discover Anticancer Drugs","volume":"29","author":"Salvador","year":"2012","journal-title":"Nat. Prod. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/nph.12325","article-title":"Bioengineering of Plant (Tri)Terpenoids: From Metabolic Engineering of Plants to Synthetic Biology in Vivo and in Vitro","volume":"200","author":"Moses","year":"2013","journal-title":"New Phytol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Xu, X., Cocco, E., Guerriero, G., Sergeant, K., Jourdan, S., Renaut, J., Hausman, J.-F., and Legay, S. (2025). Harnessing Apple Cell Suspension Cultures in Bioreactors for Triterpene Production: Transcriptomic Insights into Biomass and Triterpene Biosynthesis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073188"},{"key":"ref_16","first-page":"2127","article-title":"Paclitaxel Production through Plant Cell Culture: An Exciting Approach to Harnessing Biodiversity","volume":"70","author":"Venkat","year":"1998","journal-title":"Pure Appl. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"59","DOI":"10.5010\/JPB.2002.29.1.059","article-title":"Mass Production of Paclitaxel by Plant Cell Culture","volume":"29","author":"Choi","year":"2002","journal-title":"J. Plant Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.plaphy.2015.10.025","article-title":"Enhanced Extracellular Production of Trans-Resveratrol in Vitis Vinifera Suspension Cultured Cells by Using Cyclodextrins and Coronatine","volume":"97","author":"Almagro","year":"2015","journal-title":"Plant Physiol. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00299-011-1141-8","article-title":"Enhanced Extracellular Production of Trans-Resveratrol in Vitis Vinifera Suspension Cultured Cells by Using Cyclodextrins and Methyljasmonate","volume":"31","author":"Almagro","year":"2012","journal-title":"Plant Cell Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1007\/s002999900166","article-title":"Effect of Yeast Elicitor on the Secondary Metabolism of Ti-Transformed Salvia Miltiorrhiza Cell Suspension Cultures","volume":"19","author":"Chen","year":"2000","journal-title":"Plant Cell Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s11240-019-01592-9","article-title":"The Effects of Chitosan and Salicylic Acid on Elicitation of Secondary Metabolites and Antioxidant Activity of Safflower under in Vitro Salinity Stress","volume":"137","author":"Golkar","year":"2019","journal-title":"Plant Cell Tissue Organ. Cult."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/bit.22287","article-title":"Scale-up Analysis for a CHO Cell Culture Process in Large-Scale Bioreactors","volume":"103","author":"Xing","year":"2009","journal-title":"Biotechnol. Bioeng."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/cae.20430","article-title":"Control of Dissolved Oxygen Concentration Using Neural Network in a Batch Bioreactor","volume":"20","author":"Mete","year":"2012","journal-title":"Comput. Appl. Eng. Educ."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1109\/TLA.2014.6827863","article-title":"Effective Dissolved Oxygen Control Strategy for High-Cell-Density Cultures","volume":"12","author":"Saa","year":"2014","journal-title":"IEEE Lat. Am. Trans."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/BF00236382","article-title":"Bioreactor Studies on the Effect of Dissolved Oxygen Concentrations on Growth and Differentiation of Carrot (Daucus carota L.) Cell Cultures","volume":"11","author":"Jay","year":"1992","journal-title":"Plant Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Corbin, J.M., Hashimoto, B.I., Karuppanan, K., Kyser, Z.R., Wu, L., Roberts, B.A., Noe, A.R., Rodriguez, R.L., McDonald, K.A., and Nandi, S. (2016). Semicontinuous Bioreactor Production of Recombinant Butyrylcholinesterase in Transgenic Rice Cell Suspension Cultures. Front. Plant Sci., 7.","DOI":"10.3389\/fpls.2016.00412"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s11240-021-02009-2","article-title":"Agitation Effect on Growth and Metabolic Behavior of Plant Cell Suspension Cultures of Thevetia Peruviana at Bench Scale Reactor","volume":"145","author":"Arias","year":"2021","journal-title":"Plant Cell Tissue Organ. Cult."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4281","DOI":"10.1002\/aic.16415","article-title":"Bioreactor Scale-down Studies of Suspended Plant Cell Cultures","volume":"64","author":"Cheung","year":"2018","journal-title":"AIChE J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/0141-0229(90)90071-W","article-title":"Production of a Foreign Protein Product with Genetically Modified Plant Cells","volume":"12","author":"Hogue","year":"1990","journal-title":"Enzym. Microb. Technol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1021\/bp00016a004","article-title":"Effect of Oxygen Supply on the Suspension Culture of Genetically Modified Tobacco Cells","volume":"8","author":"Gao","year":"1992","journal-title":"Biotechnol. Prog."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s11240-019-01673-9","article-title":"Effect of Stirring Speed on the Production of Phenolic Secondary Metabolites and Growth of Buddleja Cordata Cells Cultured in Mechanically Agitated Bioreactor","volume":"139","year":"2019","journal-title":"Plant Cell Tissue Organ Cult."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s43393-023-00205-z","article-title":"Strategies and Engineering Aspects on the Scale-up of Bioreactors for Different Bioprocesses","volume":"4","author":"Herrmann","year":"2024","journal-title":"Syst. Microbiol. Biomanuf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.4014\/jmb.1307.07084","article-title":"Application of Scale-Up Criterion of Constant Oxygen Mass Transfer Coefficient (kLa) for Production of Itaconic Acid in a 50 L Pilot-Scale Fermentor by Fungal Cells of Aspergillus Terreus","volume":"23","author":"Shin","year":"2013","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1002\/btpr.2489","article-title":"A Practical Approach in Bioreactor Scale-up and Process Transfer Using a Combination of Constant P\/V and Vvm as the Criterion","volume":"33","author":"Xu","year":"2017","journal-title":"Biotechnol. Prog."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Manickavasagam, V.M., Anupindi, K., Bhatt, N., and Srivastava, S. (2025). Characterizing the Effect of Impeller Design in Plant Cell Fermentations Using CFD Modeling. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-92385-y"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ding, H., Cheng, H., Wu, J., Zhang, F., Cao, C., Mualif, S.A., and Xie, Z. (2024). A New Strategy in Bioreactor Scale-up and Process Transfer Using a Dynamic Initial Vvm According to Different Aeration Pore Size. Front. Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1461253"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1002\/cite.202100041","article-title":"Impact of Bioreactor Geometry on Mesenchymal Stem Cell Production in Stirred-Tank Bioreactors","volume":"93","author":"Petry","year":"2021","journal-title":"Chem. Ing. Tech."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11816-022-00743-3","article-title":"Brazzein Protein Production in Transgenic Carrot Cells Using Air-Lift Bioreactor Culture","volume":"16","author":"Han","year":"2022","journal-title":"Plant Biotechnol. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1002\/bit.27638","article-title":"Production of Recombinant Butyrylcholinesterase from Transgenic Rice Cell Suspension Cultures in a Pilot-Scale Bioreactor","volume":"118","author":"Macharoen","year":"2021","journal-title":"Biotechnol. Bioeng."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1007\/BF00269294","article-title":"Cultivation of Cell Cultures of Berberis Wilsonae in 20-l Airlift Bioreactors","volume":"4","author":"Breuling","year":"1985","journal-title":"Plant Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.indcrop.2014.06.036","article-title":"Optimization of Ginseng Cell Culture in Airlift Bioreactors and Developing the Large-Scale Production System","volume":"60","author":"Thanh","year":"2014","journal-title":"Ind. Crops Prod."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1111\/pbi.12428","article-title":"Large-Scale Production of Pharmaceutical Proteins in Plant Cell Culture\u2014The Protalix Experience","volume":"13","author":"Tekoah","year":"2015","journal-title":"Plant Biotechnol. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1078\/0176-1617-00576","article-title":"Taxol\u00ae and Baccatin III Production in Suspension Cultures of Taxus baccata and Taxus wallichiana in an Airlift Bioreactor","volume":"159","author":"Garden","year":"2002","journal-title":"J. Plant Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Eibl, R., and Eibl, D. (2008). Design and Use of the Wave Bioreactor for Plant Cell Culture. Plant Tissue Cult. Eng., 203\u2013227.","DOI":"10.1007\/1-4020-3694-9_12"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/elsc.202000077","article-title":"Food Ingredients and Food Made with Plant Cell and Tissue Cultures: State-of-the Art and Future Trends","volume":"21","author":"Gubser","year":"2021","journal-title":"Eng. Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"155966","DOI":"10.1016\/j.cej.2024.155966","article-title":"Mass Transfer Characteristics in Disposable Rocking Bioreactors: A Critical Review and Quantitative Data Catalogue","volume":"499","author":"Wierzchowski","year":"2024","journal-title":"Chem. Eng. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1111\/pbi.70153","article-title":"Novel Plant Cell Suspension Platforms for Saffron Apocarotenoid Production and Its Impact on Carotenoid and Volatile Profiles","volume":"23","author":"Laurel","year":"2025","journal-title":"Plant Biotechnol. J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Sukenik, S.C., Karuppanan, K., Li, Q., Lebrilla, C.B., Nandi, S., and McDonald, K.A. (2018). Transient Recombinant Protein Production in Glycoengineered Nicotiana Benthamiana Cell Suspension Culture. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041205"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Hanittinan, O., Oo, Y., Chaotham, C., Rattanapisit, K., Shanmugaraj, B., and Phoolcharoen, W. (2020). Expression Optimization, Purification and in Vitro Characterization of Human Epidermal Growth Factor Produced in Nicotiana benthamiana. Biotechnol. Rep., 28.","DOI":"10.1016\/j.btre.2020.e00524"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1111\/pbi.13834","article-title":"Custom-Made Design of Metabolite Composition in N. Benthamiana Leaves Using CRISPR Activators","volume":"20","author":"Selma","year":"2022","journal-title":"Plant Biotechnol. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/pbi.14146","article-title":"A Quantitative Autonomous Bioluminescence Reporter System with a Wide Dynamic Range for Plant Synthetic Biology","volume":"22","author":"Calvache","year":"2024","journal-title":"Plant Biotechnol. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0014-4827(68)90403-5","article-title":"Nutrient Requirements of Suspension Cultures of Soybean Root Cells","volume":"50","author":"Gamborg","year":"1968","journal-title":"Exp. Cell Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1046\/j.1365-313X.1997.12020267.x","article-title":"A Programmed Cell Death Pathway Activated in Carrot Cells Cultured at Low Cell Density","volume":"12","author":"McCabe","year":"1997","journal-title":"Plant J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1023\/A:1026500810877","article-title":"Programmed Cell Death in Cell Cultures","volume":"44","author":"McCabe","year":"2000","journal-title":"Plant Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/BF00037721","article-title":"Bioreactor Studies of the Effect of Medium pH on Carrot (Daucus carota L.) Somatic Embryogenesis","volume":"36","author":"Jay","year":"1994","journal-title":"Plant Cell Tissue Organ. Cult."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0168-9452(96)04327-O","article-title":"Effects of Initial Cell Density, pH and Dissolved Oxygen on Bioreactor Production of Carrot Somatic Embryos","volume":"115","author":"Shigeta","year":"1996","journal-title":"Plant Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s11240-022-02233-4","article-title":"Optimization of Conditions for Increasing of Saffron Cell Biomass and Crocin Production in Stirred Bioreactor","volume":"149","author":"Amini","year":"2022","journal-title":"Plant Cell Tissue Organ. Cult."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Motolin\u00eda-Alc\u00e1ntara, E.A., Castillo-Araiza, C.O., Rodr\u00edguez-Monroy, M., Rom\u00e1n-Guerrero, A., and Cruz-Sosa, F. (2021). Engineering Considerations to Produce Bioactive Compounds from Plant Cell Suspension Culture in Bioreactors. Plants, 10.","DOI":"10.3390\/plants10122762"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1002\/bit.260340806","article-title":"How Suspension Cultures of Catharanthus Roseus Respond to Oxygen Limitation: Small-Scale Tests with Applications to Large-Scale Cultures","volume":"34","author":"Snape","year":"1989","journal-title":"Biotechnol. Bioeng."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/BF00233026","article-title":"Plant Cell Growth under Different Levels of Oxygen and Carbon Dioxide","volume":"10","author":"Tate","year":"1991","journal-title":"Plant Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s11274-004-3982-6","article-title":"Production of Rosmarinic Acid byLavandula Vera MM Cell Suspension in Bioreactor: Effect of Dissolved Oxygen Concentration and Agitation","volume":"21","author":"Pavlov","year":"2005","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S0141-0229(00)00276-3","article-title":"Scale-up Study on Suspension Cultures of Taxus Chinensis Cells for Production of Taxane Diterpene","volume":"27","author":"Pan","year":"2000","journal-title":"Enzyme Microb. Technol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"10893","DOI":"10.1021\/acs.iecr.3c00736","article-title":"Mass Transfer in a Liter-Scale Wave Mixed Single-Use Bioreactor: Influence of Viscosity and Antifoaming Agent","volume":"62","author":"Bartczak","year":"2023","journal-title":"Ind. Eng. Chem. Res."},{"key":"ref_64","first-page":"55","article-title":"Bag Bioreactor Based on Wave-Induced Motion: Characteristics and Applications","volume":"115","author":"Eibl","year":"2009","journal-title":"Adv. Biochem. Eng. Biotechnol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/bit.22061","article-title":"Bioreactor Strategies for Improving Production Yield and Functionality of a Recombinant Human Protein in Transgenic Tobacco Cell Cultures","volume":"102","author":"Huang","year":"2009","journal-title":"Biotechnol. Bioeng."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/elsc.201800134","article-title":"Production of Anti-Inflammatory Compounds in Sphaeralcea Angustifolia Cell Suspension Cultivated in Stirred Tank Bioreactor","volume":"19","year":"2019","journal-title":"Eng. Life Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s00449-022-02700-4","article-title":"Enhanced Production of Bacopa Saponins by Repeated Batch Strategy in Bioreactor","volume":"45","author":"Sahoo","year":"2022","journal-title":"Bioprocess Biosyst. Eng."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Kargupta, R., Rivera, S., Kochert, B., Devenney, K., Donelly, D., Atieh, T., Li, F., Pan, J., Patel, D., and Tayi, V. (2025). Elucidation of Cell Culture Impacts on Hydroxylysine Levels in Monoclonal Antibodies Using High-Throughput Analytical Quantification and Media Components. Biotechnol. Prog.","DOI":"10.1002\/btpr.70068"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Andaluz, A., Monteverde, B., Vera, K., Tse, B., Gajic, I., Forelich, C., and Motevalian, S.P. (2025). Accelerated Adeno Associated Virus Upstream Process Development from High-Throughput Systems to Clinical Scale. Biotechnol. Bioeng.","DOI":"10.1002\/bit.70052"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Zhang, X., Moroney, J., Hoshan, L., Jiang, R., and Xu, S. (2019). Systematic Evaluation of High-Throughput Scale-down Models for Single-Use Bioreactors (SUB) Using Volumetric Gas Flow Rate as the Criterion. Biochem. Eng. J., 151.","DOI":"10.1016\/j.bej.2019.107307"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00449-013-1001-8","article-title":"Modeling of Gas\u2013Liquid Mass Transfer in a Stirred Tank Bioreactor Agitated by a Rushton Turbine or a New Pitched Blade Impeller","volume":"37","author":"Gelves","year":"2014","journal-title":"Bioprocess Biosyst. Eng."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/bit.260370410","article-title":"An Investigation into the Role of Initial KLa on the Growth and Alkaloid Accumulation by Cultures of Catharanthus Roseus","volume":"37","author":"Leckie","year":"1991","journal-title":"Biotechnol. Bioeng."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1021\/bp00032a004","article-title":"Cell Damage and Oxygen Mass Transfer during Cultivation of Nicotiana Tabacum in a Stirred-Tank Bioreactor","volume":"11","author":"Ho","year":"1995","journal-title":"Biotechnol. Prog."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1021\/bp990042v","article-title":"Design of Mixing Systems for Plant Cell Suspensions in Stirred Reactors","volume":"15","author":"Doran","year":"1999","journal-title":"Biotechnol. Prog."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev-phyto-080417-050141","article-title":"The Rise and Rise of Nicotiana Benthamiana: A Plant for All Reasons","volume":"56","author":"Bally","year":"2018","journal-title":"Annu. Rev. Phytopathol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/j.1399-3054.1962.tb08052.x","article-title":"A Revised Medium for Rapid Growth and Bio Assays with Tobacco Tissue Cultures","volume":"15","author":"Murashige","year":"1962","journal-title":"Physiol. Plant."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/bit.22713","article-title":"Semicontinuous Bioreactor Production of a Recombinant Human Therapeutic Protein Using a Chemically Inducible Viral Amplicon Expression System in Transgenic Plant Cell Suspension Cultures","volume":"106","author":"Huang","year":"2010","journal-title":"Biotechnol. Bioeng."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1002\/bit.260290810","article-title":"A Simple Na2SO3 Feeding Method for KLa Measurement in Large-Scale Fermentors","volume":"29","author":"Imai","year":"1987","journal-title":"Biotechnol. Bioeng."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"106776","DOI":"10.1016\/j.foodhyd.2021.106776","article-title":"Modelling Shear Viscosity of Soft Plant Cell Suspensions","volume":"118","author":"Leverrier","year":"2021","journal-title":"Food Hydrocoll."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/wics.147","article-title":"Ggplot2","volume":"3","author":"Wickham","year":"2011","journal-title":"Wiley Interdiscip. Rev. Comput. Stat."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/14\/18\/2879\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:31Z","timestamp":1760035591000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/14\/18\/2879"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,16]]},"references-count":80,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["plants14182879"],"URL":"https:\/\/doi.org\/10.3390\/plants14182879","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,16]]}}}