Use of regulated secretion in protein production from animal cells: an overview

Traditional industrial cell culture processes require extensive downstream product refining due to low product titer and purity in the spent growth medium. A controlled secretion process incorporating cells derived from endocrine or exocrine organs could potentially alleviate this processing burden by dynamically decoupling product recovery from cell growth and product biosynthesis. In addition, such specialized secretory cells may be uniquely capable of performing desirable post-translational processing of the secretory product. We briefly review the biology of regulated protein secretion as well as the biology and biochemistry of the signal transduction mechanisms by which regulated systems respond to environmental stimuli. Drawing on these and other basic principles from cell biology and bioengineering, we describe the important features of a controlled secretion process. Among other issues we discuss the choice of cell lines, expression systems, cell culture methods, and bioreactor configurations. We extensively analyze the kinetics of regulated secretion in the context of a controlled secretion process. This discussion is illustrated with experimental results from two model cell lines, recombinant AtT-20 and beta TC3, expressing recombinant human endocrine hormones or native murine insulin respectively.