title: CellMAC: a novel technology for encapsulation of mammalian cells in cellulose sulfate/pDADMAC capsules assembled on a transient alginate/Ca2+ scaffold.
abstract: Microencapsulation of desired mammalian cell phenotypes in biocompatible polymer matrices represents a powerful technology for cell-based therapies and biopharmaceutical manufacturing of protein therapeutics. We have pioneered a novel jet break-up-compatible process for encapsulation of mammalian cells in cellulose sulfate (CS)/poly-diallyl-dimethyl-ammoniumchloride (pDADMAC) (CellMAC) capsules. CS and pDADMAC polymerize on a transient ad hoc co-assembled Ca2+/alginate scaffold and form homogenous capsules following dissolution of the alginate core by Ca2+ chelating agents. CellMAC capsules exhibited excellent mechanical properties and showed a molecular weight cut-off between 43 and 77kDa. Chinese hamster ovary cells engineered for constitutive production of the glycohormone erythropoietin reached high viable cell densities when grown inside CellMAC capsules, while specific erythropoietin (EPO) productivities matched those of conventional non-encapsulated control cultures. CellMAC-encapsulated EPO-production cell lines induced increased EPO serum levels when implanted intraperitoneally into mice and provided robust glycoprotein production during standard stirred-tank bioreactor operation. We expect the CellMAC technology to foster advances in therapeutic encapsulation of engineered cell lines as well as manufacturing of protein pharmaceuticals.
authors.affiliation: Institute of Biotechnology, Swiss Federal Institute of Technology, ETH Hoenggerberg, CH-8093 Zurich, Switzerland.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Weber
authors.forename: Matthias
authors.initials: M
authors.lastname: Rinderknecht
authors.forename: Marie
authors.initials: M
authors.lastname: Daoud-El Baba
authors.forename: François-Nicolas
authors.initials: FN
authors.lastname: de Glutz
authors.forename: Dominique
authors.initials: D
authors.lastname: Aubel
authors.forename: Martin
authors.initials: M
authors.lastname: Fussenegger
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D019149:Bioreactors; D016466:CHO Cells; D002214:Capsules; D049109:Cell Proliferation; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry*; D006224:Cricetinae; D003412:Cricetulus; D004339:Drug Compounding / Q000379:methods*; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry*; D006603:Hexuronic Acids / Q000737:chemistry*; D008322:Mammals; D051379:Mice; D008815:Mice, Inbred Strains; D011095:Polyethylenes / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000464:Alginates; D002214:Capsules; D006603:Hexuronic Acids; D011095:Polyethylenes; D000644:Quaternary Ammonium Compounds; D011994:Recombinant Proteins; D004921:Erythropoietin; C041004:poly-N,N-dimethyl-N,N-diallylammonium chloride; D020723:Glucuronic Acid; D002482:Cellulose; C020254:cellulose sulfate