Growth factors play a critical role in media optimization, contributing to long-term growth and rapid proliferation of cell lines in serum-free media formulations.
MEDIA OPTIMIZATION - GROWTH FACTORS
Optimizing cell culture growth and productivity is the primary goal in cell culture expansion.
Serum has historically been the most common additive to cell culture media. It adds essential components, such as hormones and growth factors. However, its undefined animal origin poses significant contamination risk with adventitious agents.
While serum-free formulations are chemically-defined, they show increased oxidative stress and cell death. Growth factors can alleviate that stress and are critical for long-term growth and proliferation of many cell lines in serum-free media formulations.
Recombinant proteins, manufactured exclusively for cell culture applications, have been shown to boost the productivity of a chemically-defined medium.The formulations are well-defined and they are manufactured following strict GMP quality conditions with a secure supply chain. Two common cell growth factors are:
Insulin supports the serum-free growth of many cell types. The low potency of insulin has been attributed to signaling through the IGF-I receptor instead of its own receptor. The activation of the IGF-I receptor has been shown to mediate potent proliferation and anti-apoptotic pathways.
A more potent growth factor, such as LONG®R3 IGF-I, targets and activates the IGF-I receptor with greater specificity. The more effective activation of the IGF-I receptor by LONG®R3 IGF-I allows for significantly less protein supplementation and, therefore, less potential impact on downstream processing.
LONG®R3 IGF-I CELL CULTURE GROWTH FACTOR
LONG® technology consists of a fusion of the growth factor with a portion of growth hormone sequence. The fusion improves growth factor production without imparting its biological activity.
A distinct biological advantage
All mammalian cells secrete IGF Binding Proteins (IGFBPs) which bind to and inhibit native IGF-I. The substitution of an arginine for glutamic acid at position three in LONG®R3IGF-I, in conjunction with the 13 amino acid N-terminal extension peptide, results in > 1000 fold reduced affinity for IGFBPs, enhancing its bio-availability and effectiveness in comparison to native IGF-I.
Specificity is the key to increased productivity
Unlike insulin, LONG®R3IGF-I specifically targets and activates the type I IGF Receptor (IGF-IR) resulting in greater activation of downstream signaling cascades responsible for proliferation and inhibiting apoptosis. Greater activation of these key pathways results in increased cell density, higher viability and extended cell culture productivity.
SAFC® is the exclusive worldwide distributor of LONG®R3 IGF-I for industrial cell culture applications.
LONG®R3 IGF-I has been shown to improve volumetric productivity in CHO cell culture by up to 62% over cell culture with no supplementation and 40% over cell culture supplemented with insulin.