In the early 1980s, I worked in a tissue-culture lab where scientists grew chicken neurons and muscle cells on cover slips coated in rat-tail collagen. Yes, we used collagen isolated in-house—by me—from actual rats’ tails. Although growing cells in monolayers on a solid surface was common then, some scientists already wanted to culture cells in suspension.
In 1967, Anton van Wezel—a microbial engineer in the department of vaccine production at the Rijksinstituut voor Volksgezondheid in Utrecht, the Netherlands—reported: “There are obvious advantages in culturing tissue cells in suspension instead of in monolayers in using the suspension as a substrate for virus multiplication.”
To grow enough cells in suspension, though, the cells needed to hold onto something. So, van Wezel’s team supplemented cultures with small particles made of the polymer dextran, and it worked. These particles—named “micro-carriers” by van Wezel—were even used in improving the production of polio vaccines.
Even after more than 50 years of using microcarriers in culturing and bioprocessing, though, Majid Ebrahimi Warkiani, PhD, a professor in the school of biomedical engineering at the University of Technology Sydney in Australia, and his colleagues recently noted that “innovation in this sector has been limited, leading to challenges in industrial scaling.”
Custom carriers
Part of the problem, according to Warkiani’s team, is the lack of fit-for-purpose microcarriers. “Customizability is crucial as different cell types require specific physical and chemical substrate properties; an aspect inadequately addressed in current microcarrier technology,” these scientists pointed out. “Research has extensively shown that cell growth, secretion, and differentiation are significantly influenced by substrate properties.”
To create custom microcarriers, Warkiani worked with Smart MCs, a biotechnology company based in Ultimo, Australia. The microcarriers used were 150 micrometers in diameter and their stiffness and surface charges could be adjusted. From this research on various cell types, Warkiani and his colleagues pointed out that “Experimental data showed a strong correlation between microcarrier stiffness and cell proliferation.”
In some cases, pairing the cells with the best microcarriers increased cell yields by more than 20-fold.
“Aligning microcarrier characteristics with specific requirements ensured improved cell growth,” concluded the scientists. Such alignment was not possible when growing cells on rat-tail collagen, and microcarriers are certainly much easier to obtain.
