title: Bioreactor engineering using disposable technology for enhanced production of hCTLA4Ig in transgenic rice cell cultures.
abstract: Two kinds of disposable bioreactors, air-lift disposable bioreactors (ADB) and wave disposable bioreactors (WDB) were compared with stirred-tank reactors (5-L STR). These bioreactors were successfully applied to transgenic rice cell cultures for the production of recombinant human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig). In both systems, a fed-batch culture method was used to produce hCTLA4Ig efficiently by feeding concentrated amino acids and production levels were enhanced when dissolved oxygen (DO) level was regulated at 30% using pure oxygen sparging. Agitation and aeration rate during cultivation in ADB and WDB were determined by the same mixing time. The results in both disposable bioreactors showed similar values in maximum cell density (11.9 gDCW/L and 12.6 gDCW/L), doubling time (4.8- and 5.0-day), and maximum hCTLA4Ig concentration (43.7 and 43.3 mg/L). Relatively higher cell viability was sustained in the ADB whereas hCTLA4Ig productivity was 1.2-fold higher than that in WDB. The productivity was improved by increasing aeration rate (0.2 vvm). Overall, our experiments demonstrate pneumatically driven disposable bioreactors are applicable for the production of recombinant proteins in plant cell cultures. These results will be useful for development and scale-up studies of disposable bioreactor systems for transgenic plant cell cultures.
authors.affiliation: Department of Biological Engineering, Inha University, Incheon, Korea.
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Kwon
authors.forename: Yong-Suk
authors.initials: YS
authors.lastname: Yang
authors.forename: Su-Hwan
authors.initials: SH
authors.lastname: Cheon
authors.forename: Hyung-Jin
authors.initials: HJ
authors.lastname: Nam
authors.forename: Gi-Hong
authors.initials: GH
authors.lastname: Jin
authors.forename: Dong-Il
authors.initials: DI
authors.lastname: Kim
mesh_terms: D000069594:Abatacept; D019149:Bioreactors; D001709:Biotechnology; D002470:Cell Survival; D006801:Humans; D018796:Immunoconjugates / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012275:Oryza / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011994:Recombinant Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D018796:Immunoconjugates; D011994:Recombinant Proteins; D000069594:Abatacept; D010100:Oxygen
keywords: bioreactor engineering; disposable bioreactor; mass and oxygen transfer; plant-specific bioprocess; transgenic rice cell cultures