Article: A 3D collagen microsphere culture system for GDNF-secreting HEK293 cells with enhanced protein productivity

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TitleA 3D collagen microsphere culture system for GDNF-secreting HEK293 cells with enhanced protein productivity
AuthorsWong, HL2
Wang, MX1
Cheung, PT1
Yao, KM1
Chan, BP2
Keywords3D culture
Biopharmaceutical manufacturing
Collagen
GDNF-secreting HEK293 cells
Microencapsulation
Microsphere
Issue Date2007
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/biomaterials
CitationBiomaterials, 2007, v. 28 n. 35, p. 5369-5380 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.biomaterials.2007.08.016
AbstractMammalian cell culture technology has been used for decades in mass production of therapeutic proteins. However, unrestricted cell proliferation usually results in low-protein productivity. Controlled proliferation technologies such as metabolism intervention and genetic manipulation are therefore applied to enhance the productivity. Nevertheless, these strategies induced growth arrest with reduced viability and increased apoptosis. In this study, we report a new controlled proliferation technology by encapsulating human embryonic kidney (HEK) 293 cells over-expressing glial-derived neurotrophic factor (GDNF) in 3D collagen microspheres for extended culture. We investigated the viability, proliferation, cell cycle and GDNF productivity of HEK293 cells in microspheres as compared to monolayer culture. This system provides a physiologically relevant tissue-like environment for cells to grow and exerts proliferation control throughout the culture period without compromising the viability. A significant increase in the production rate of GDNF was found in the 3D microsphere system comparing with the monolayer culture. GDNF productivity was also significantly affected by the initial cell number and the serum concentration. The secreted GDNF was still bioactive as it induced neurite extension in PC12 cells. In summary, the 3D collagen microsphere system presents a cost-effective controlled growth technology for protein production in pharmaceutical manufacturing. © 2007 Elsevier Ltd. All rights reserved.
ISSN0142-9612
2011 Impact Factor: 7.404
2011 SCImago Journal Rankings: 0.633
DOIhttp://dx.doi.org/10.1016/j.biomaterials.2007.08.016
ISI Accession Number IDWOS:000250860000016
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorWong, HL
dc.contributor.authorWang, MX
dc.contributor.authorCheung, PT
dc.contributor.authorYao, KM
dc.contributor.authorChan, BP
dc.date.accessioned2010-09-06T06:03:27Z
dc.date.available2010-09-06T06:03:27Z
dc.date.issued2007
dc.description.abstractMammalian cell culture technology has been used for decades in mass production of therapeutic proteins. However, unrestricted cell proliferation usually results in low-protein productivity. Controlled proliferation technologies such as metabolism intervention and genetic manipulation are therefore applied to enhance the productivity. Nevertheless, these strategies induced growth arrest with reduced viability and increased apoptosis. In this study, we report a new controlled proliferation technology by encapsulating human embryonic kidney (HEK) 293 cells over-expressing glial-derived neurotrophic factor (GDNF) in 3D collagen microspheres for extended culture. We investigated the viability, proliferation, cell cycle and GDNF productivity of HEK293 cells in microspheres as compared to monolayer culture. This system provides a physiologically relevant tissue-like environment for cells to grow and exerts proliferation control throughout the culture period without compromising the viability. A significant increase in the production rate of GDNF was found in the 3D microsphere system comparing with the monolayer culture. GDNF productivity was also significantly affected by the initial cell number and the serum concentration. The secreted GDNF was still bioactive as it induced neurite extension in PC12 cells. In summary, the 3D collagen microsphere system presents a cost-effective controlled growth technology for protein production in pharmaceutical manufacturing. © 2007 Elsevier Ltd. All rights reserved.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationBiomaterials, 2007, v. 28 n. 35, p. 5369-5380 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.biomaterials.2007.08.016
dc.identifier.doihttp://dx.doi.org/10.1016/j.biomaterials.2007.08.016
dc.identifier.epage5380
dc.identifier.hkuros145968
dc.identifier.isiWOS:000250860000016
dc.identifier.issn0142-9612
2011 Impact Factor: 7.404
2011 SCImago Journal Rankings: 0.633
dc.identifier.issue35
dc.identifier.openurl
dc.identifier.pmid17764735
dc.identifier.scopuseid_2-s2.0-34948825863
dc.identifier.spage5369
dc.identifier.urihttp://hdl.handle.net/10722/68318
dc.identifier.volume28
dc.languageeng
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/biomaterials
dc.publisher.placeNetherlands
dc.relation.ispartofBiomaterials
dc.relation.referencesReferences in Scopus
dc.rightsBiomaterials. Copyright © Elsevier BV.
dc.subject.meshAnimals
dc.subject.meshCell Culture Techniques - methods
dc.subject.meshCell Line
dc.subject.meshCollagen Type I
dc.subject.meshGlial Cell Line-Derived Neurotrophic Factor - biosynthesis - secretion
dc.subject.meshHumans
dc.subject.meshKidney - cytology - secretion
dc.subject.meshMice
dc.subject.meshMicrospheres
dc.subject.meshPC12 Cells
dc.subject.meshRats
dc.subject.meshRecombinant Proteins - biosynthesis - secretion
dc.subject3D culture
dc.subjectBiopharmaceutical manufacturing
dc.subjectCollagen
dc.subjectGDNF-secreting HEK293 cells
dc.subjectMicroencapsulation
dc.subjectMicrosphere
dc.titleA 3D collagen microsphere culture system for GDNF-secreting HEK293 cells with enhanced protein productivity
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Faculty of Engineering