Researchers have created a highly affordable formula for a human stem cell growth medium that could save labs millions of dollars in reagent costs and eliminate the need for weekend "feeding" of stem cells.
The formula, described in a patent application published by the U.S. Patent and Trademark Office on March 25, can be produced with reagents that cost just 3% of the average cost of commercial media, according to an accompanying study in Stem Cell Reports. Reagents are the hormones and other biomolecules required to grow the cells.
"We knew we needed to develop a protocol where everything was cheap and anyone could make it," said inventor Paul Burridge, an assistant professor of pharmacology at Northwestern University.
The work also takes a bold step forward in ensuring that all labs have access to the best materials for stem cell culture, which is prohibitively expensive for many labs, despite its incredible utility in medical and biological research.
"Pluripotent stem cells are a human genome captured in culture. It's the ultimate tool," Burridge said. "I think all stem cell labs should use exactly the same technology. We should all use the best things that are most cost-effective."
As the scope of stem cell research increases, researchers such as Burridge are also more frequently relying on high numbers of stem cells to complete their experiments, further increasing the demand for affordable, high-quality culture supplies.
"We're now moving on from doing these boutique little experiments where we have a few plates of cells, to the sorts of projects we do in my lab, where we have 100 stem cell lines," Burridge said.
All cell culture requires an appropriate medium to grow the target cells without also becoming host to colonies of experiment-ruining bacteria. Stem cell culture relies on a delicate balance of nutrients, growth factors and buffers to control pH. And while it's technically possible for labs to make their own stem cell growth media, this isn't always efficient.
"A lot of the commercial media that are available all come from academic labs originally," Burridge said. "Then, as academics, we're trying to be as efficient with our time as possible, and that means that in some cases, people are willing to pay exorbitant prices for commercial media."
As part of their study, Burridge and his team compiled the costs of different commercial media formulations, finding that they typically cost between $450 and $550 per liter.
Their formula costs just $16 per liter to make. And, unlike many commercial formulations, the medium can last several days without needing to be changed, eliminating the need for "weekend feeding" for cultured cells.
The major leap for the team in reducing the cost of producing stem cell media was finding a way to source recombinant proteins, which are engineered in the lab from modified DNA. These proteins include important growth factors for stem cells, but they are also difficult to make, driving up the cost of commercial versions of these proteins and of commercial media as a whole.
The team produced its own recombinant proteins using E. coli bacteria as a host to grow the required DNA. The researchers also employed a few cheaper commercial products themselves to simplify the process, including media to grow the bacteria and tools to extract and purify DNA. This also eliminated the need for certain specialized chromatography procedures that may also be a barrier for some labs.
"Scientists that are good at cell culture are not necessarily that good at recombinant protein production, so there's some complexity there," Burridge said. "We had to really simplify these things."
The team has licensed the invention to a startup called Defined Bioscience. The company's version of the medium, HiDef-B8, is currently undergoing tests by the researchers. It is also available as a supplement that can be added to a base medium.
Burridge explained that while HiDef-B8 will be less expensive than standard commercial media, the researchers also encourage labs to save by making their own media using their protocol when feasible, particularly since most formulas for media got their start in academic labs before being produced more widely.
"You do need to democratize these kinds of products, especially because they come from academic research and [the products] kind of leave, and then academics are kind of stuck with the bill," he said.
For now, Burridge and his lab will be using plenty of culture media as they continue to use hundreds of stem cell lines in their work on pharmacogenetics, the study of genetic-based differences in drug response.
They are also working on methods to produce cultivated meat because he feels that there are many worthwhile pursuits his invention could be applied to.
Burridge hopes that their stem cell medium will allow them to one day "make something that's cheaper with the same organoleptic properties [as meat]. Save the environment, reduce what you eat, [and] your land usage. That's just as much of a noble task as what we do with pharmacogenomics, I feel."
The application for the patent, "Cost effective culture media and protocol for human induced pluripotent stem cells," was filed Sept. 18 to the U.S. Patent and Trademark Office. It was published March 25 with the application number 2021/0087525. The earliest priority date was Sept. 19, 2019. The inventor of the pending patent is Paul Burridge, Northwestern University.