Growth and Productivity of NS0 Cells with Nanoparticle Cholesterol Supplementation

Providing lipids to cells in culture is a challenge because of the low solubility of lipids in aqueous medium. Limited loading capacity, precipitation, instability and toxicity are associated with traditional delivery methods that involve solvents or carrier molecules. In this work, nanoparticle cholesterol mixtures (NCM) were produced by electrohydrodynamic spraying and added directly to a cholesterol auxotroph NS0 cell line without using any solvents or carrier molecules. Compared to a conventional cholesterol solution, SyntheChol^TM NS0 supplement, NCM are significantly less cytotoxic. In a fed batch cell culture process, product titer was increased by 32% when the NCM supplement replaced SyntheChol^TM NS0 supplement. The highest product titer was achieved when both NCM and SyntheChol^TM NS0 supplements were fed in the fed-batch process. However, challenges of efficiently delivering cholesterol in the form of nanoparticles still exist in the long term subculture of NS0 cells.