Report

Inhibitory effects of persistent apoptotic cells on monoclonal antibody production in vitro: Simple removal of non-viable cells improves antibody productivity by hybridoma cells in culture

Volume 1, Issue 4   July/August 2009
Pages 370 - 376
http://dx.doi.org/10.4161/mabs.1.4.9124
Authors: Christopher D. Gregory, John D. Pound, Andrew Devitt, Megan Wilson-Jones, Parthasarathi Ray and Ruth J. Murray

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Abstract:

Cells undergoing apoptosis in vivo are rapidly detected and cleared by phagocytes. Swift
recognition and removal of apoptotic cells is important for normal tissue homeostasis
and failure in the underlying clearance mechanisms has pathological consequences
associated with inflammatory and auto-immune diseases. Cell cultures in vitro usually
lack the capacity for removal of non-viable cells because of the absence of phagocytes
and, as such, fail to emulate the healthy in vivo micro-environment from which dead cells
are absent. While a key objective in cell culture is to maintain viability at maximal levels,
cell death is unavoidable and non-viable cells frequently contaminate cultures in
significant numbers. Here we show that the presence of apoptotic cells in monoclonal
antibody-producing hybridoma cultures has markedly detrimental effects on antibody
productivity. Removal of apoptotic hybridoma cells by macrophages at the time of
seeding resulted in 100% improved antibody productivity that was, surprisingly to us,
most pronounced late on in the cultures. Furthermore, we were able to recapitulate this
effect using novel super-paramagnetic Dead-Cert™Nanoparticles to remove non-viable
cells simply and effectively at culture seeding. These results (1) provide direct evidence
that apoptotic cells have a profound influence on their non-phagocytic neighbours in
culture and (2) demonstrate the effectiveness of a simple dead-cell removal strategy for
improving antibody manufacture in vitro.

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