Cell Cultivation System on the Basis of Porous Ceramic for the Production of Virus-Like Particles

Abstract

The production of virus-lilce particles (VLP) is based on the expression of human Polyomavirus (JCV)-VP1 in anchorage-dependent insect cells SF-158 using recombinant baculoviruses. To use these VLPs in future in clinical trials as an efficient delivery system for gene therapy it is necessary to establish a large scale production. For this purpose a new cultivation system basing on the attachment of cells onto macroporous ceramic in a special flow chamber was developed. On these ceramics insect cells form multicellular monolayers. During cell growth and baculovirus infection cells were fed with aerated, tempered and pH-controlled medium from a reservoir. The process is monitored by measuring the oxygen consumption (online), the glucose consumption and viable cell counts (both: offline). Testing two different flow chambers with fitting ceramics, one squared ceramic and one cylindrical honeycomed ceramic with a corresponding larger growth surface, the optimal medium flow, the doubling time and the attachment of the cells were determined. The cells grew in this cultivation system as well as in cell culture flasks and the surface correlated productivity increased approximately eighty-fold.