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Trends I’m seeing in the cell culture space lately:
→ AI meets biology is accelerating the already-in-progress trend towards chemically defined research tools. This is logical. If you’re training models using cell culture data, you want the inputs as clean and consistent as possible. For example, this makes the variability introduced by FBS more noticeable as well as problematic. → Completely anecdotal but there seem to be some bad batches of FBS circulating. I’m hearing from scientists who have used fetal bovine serum for years, but suddenly - despite certificates of analysis and in-house batch testing - their latest batch is testing positive for problematic viruses or has heavy precipitation/flocculants. → Cell culture media optimisation platforms are becoming more and more advanced. The result is highly specialised cell culture media built for specific cell types allowing for faster proliferation rates, cheaper costs per liter, and higher densities than ever. → Despite these advanced cell culture media, there are plenty of scientists looking for “this is easy to use and it grows the six different types of cells that my lab grows” instead. Knock out serum replacement (KSR) seems to be the best known "serum replacement", which is kind of interesting because it was designed primarily for pluripotent stem cells and usually doesn’t substitute well for serum in most other cell types. → In this vein: there’s increasingly a natural split between “exploratory biology media” and “production media.” Highly optimized, specialised media are necessary for high densities or cost optimisation at huge scales. But for exploratory work, operational simplicity is important; a single formulation that reliably grows a variety of cells and is sufficiently forgiving of handling variation is valuable. → Adherence is a sticking point (hah, I amuse myself anyway). In most serum-free media systems, coating plates with adherence proteins is the standard. This is operationally annoying relative to culturing adherent cells with serum-containing media. (Let’s do something about this, why don’t we? 😉)
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Hey New Zealand scientists, FRS Pioneer is travelling across the ditch! This year, Beyond Animal Research is supporting NZ scientists in accessing Media City Scientific’s FBS replacement. The first shipments have already landed on NZ soil and we’ll be working together to develop additional case studies showing how scientists can easily replace FBS with a chemically defined, animal-origin-free alternative for cell culture or cryopreservation. Being animal free AND being able to reproducibly control exactly what’s in your cell culture media makes this a win-win for everyone. Thanks Tara Jackson and the BAR team for making this happent! Are you a NZ scientist keen on using FRS Pioneer in your research or teaching? You can get involved by emailing [email protected]. Cheers ☺️  Most cell culture troubleshooting focuses on what you might be doing wrong, while less attention goes to what FBS is correcting for in the background. That's something worth understanding when a batch behaves unexpectedly, or when you try to replace FBS entirely.
FBS is a remarkably effective antioxidant buffer. Not because it was human-designed to be so; it's a biological fluid, it just comes that way. But that function matters and it's almost never replaced when scientists DIY a serum-free cell culture media. Most scientists think of FBS mostly as a source of growth factors and nutrients, but it also contains a sophisticated antioxidant pool that buffers the oxidative environment your cells are living in. Most serum-free formulations replace some of this, usually in the form of albumin, transferrin, and a selenium source, but there's considerably more to antioxidant buffering than that. Strip out the wider pool without replacement and subtle shifts in ROS levels start affecting mitochondrial function, altering proliferation rates, and in sensitive cell types pushing cells toward senescence prematurely. These aren't dramatic phenotypes and you probably won't notice them immediately under the microscope. Instead, they usually show up as variability. I frequently joke that FBS covers all manner of sins. It's forgiving in part because its antioxidant buffering absorbs a lot of handling variation: trypsin left on slightly too long, feeding with cold media, a suboptimal seeding density, media that's been in the fridge a month. But that buffering capacity isn't consistent between batches. Albumin, transferrin, selenium, tocopherols, and others - these are all biological and fluctuate with the source animal's condition, age, and processing. It's also a parameter that's not usually measured during batch testing. Defined media tends to be more honest, because it reflects exactly what you give it. This is a real advantage, but only if the antioxidant pool has been engineered carefully. Get it wrong and you've traded one source of variability for another, potentially more confusing one. This is why we spent a full year in external pilot testing before bringing our chemically defined FBS replacement to market, including trialing with students. We saw what happened when different passaging reagents, seeding densities, experience levels, and protocols were applied to one reagent. Some things broke. We made the product more robust wherever we could, and where specific handling processes were necessary, we documented it clearly. A formulation that can't handle real-world variation has no business replacing something as forgiving as FBS. Takeaway: antioxidant buffering is one of the most overlooked variables in cell culture, whether you're troubleshooting batch-to-batch inconsistency in FBS or building out a serum-free formulation. Something to pay attention to! And as always, more reading below if you want to dive deeper 😊 Roche M et al. (2008) covers the antioxidant properties of serum albumin - https://pubmed.ncbi.nlm.nih.gov/18474236/ Barry Halliwell has written extensively on ROS, Fenton chemistry, and biological antioxidant systems. His work is definitely some to check out if you’re interested in this space! One of his papers to get you started: https://www.sciencedirect.com/science/article/pii/S0014579303002357 |
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