Doctoral student Robert Skolik and Associate Professor Michael Menze, in the Department of Biology at the University of Louisville, have found a way to make cell cultures respond more closely to normal cells, allowing drugs to be screened for toxicity earlier in the research timeline.

The vast majority of cells used for biomedical research are derived from cancer tissues stored in biorepositories. They are cheap to maintain, easy to grow and multiply quickly. Specifically, liver cancer cells are desirable for testing the toxicity of drugs for any number of diseases.

“You like to use liver cells because this is the organ that would detoxify whatever drug for whatever treatment you are testing,” Menze said. “When new drugs are being developed for diabetes or another disease, one of the concerns is whether they are toxic to the liver.”

The cells do come with limitations, however. Since they are cancer cells, they may not be as sensitive to toxins as normal cells, so they may not reveal issues with toxicity that can appear much later in the drug testing process.

Skolik and Menze have discovered that by changing two components of the media used to culture the cells, they can make liver cancer cells behave more like normal liver cells. Rather than using standard serum containing glucose, they used serum from which the glucose had been removed using dialysis and added galactose – a different form of sugar – to the media. The tumor cells metabolize galactose at a much slower rate than glucose. This changes the metabolism of the cells making them behave more like normal liver cells.

By using cells cultured with this modified serum, drugs may effectively be screened for toxicity earlier in the research process, possibly saving millions of dollars.

“It started just as a way to sensitize cells to mitochondrial activity, the cellular powerhouse, but then we realized we had a way to investigate how we are shifting cancer metabolism,” Skolik said. “In short, we have found a way to reprogram cancer cells to look – and act – more like normal cells.”

The research is featured on the cover of the April issue of . The cover image was the work of Nilay Chakraborty and Jason Solocinski at the University of Michigan-Dearborn, who developed a new process to obtain live images of the distribution of energy molecules in cells, showing how cells respond to changes in the cell culture conditions.

To fully realize the effect he reported, Skolik also cultured the cells for a longer period of time than usual.

“In the past, people would do a 12-hour adaptation to this new media. But what we showed is if you culture them for 4 to 5 weeks, you have a much more robust shift,” Skolik said. “When it comes to gene expression, you get much more bang for the buck when you adapt them for a longer period.”

Although the modified serum for the cultures requires the additional step of dialysis and longer culture time, it can yield benefits at later testing stages.

“You would reserve this process for key experiments or toxicity screening,” Menze said. “However, if you go into a Phase 1 clinical trial and find toxicity there, it is way more expensive than using this method.”

At this month’s Beer with a Scientist, Michael Menze, PhD, associate professor in the Department of Biology at the University of Louisville, will discuss how the mechanisms behind these animals’ survival in impossible conditions can be used to transform human medicine.

“I am fascinated with how these animals can survive the limits of life, so my research focuses on decoding the molecular mechanisms that protect animals exposed to harsh environmental factors,” Menze said. “Understanding how life can survive these intense insults allows us to solve medical challenges ranging from long-duration space travel to securing the human blood supply.”

Menze’s talk begins at 7 p.m. on Wednesday, Oct. 16, at , 8023 Catherine Lane. A 30-minute presentation will be followed by an informal Q&A session.

To solve that problem, researchers at the University of Louisville have for loading preservative compounds into red blood cells. This technology may aid in extending blood’s window of use by enabling the dehydration and dry storage of red blood cells at room temperature.

Now, via a $750,000 from the National Science Foundation (NSF) and a cooperative agreement with Indianapolis-based Cook Regentec, the team is working on further developing the technology and getting it to market.

“The goal is that this kind of system could be commercialized,” said Dr. Jonathan Kopechek, an assistant professor of bioengineering. “There’s a whole lot of opportunity. It’s exciting.”

Drs. Kopechek and Michael Menze, and graduate student Brett Janis, invented the technology and developed the prototype – a small, chamber with fluid channels inside. They are working with the to commercialize and protect the intellectual property.

“The researchers have proven it works and they have the prototype,” said Dr. Paula Bates, a UofL professor of medicine, who teamed up with the inventors to secure this grant as principal investigator.

By creating temporary breaks in the cell walls with tiny bubbles and ultrasound, the team can inject a preservative that protects the cell membranes. Once loaded with that preservative, the cells are ready for dehydration. Then, the blood can be rehydrated on-demand — even months later.

The process is sort of like dehydrating sea monkeys, then watching them spring back to life when they’re submerged in an aquarium.

“The dehydrated red blood cells can be reconstituted by gently mixing with water,” said Menze, an associate professor of biology and assistant chair. “It’s that simple: ’just add water’.”

Much of the initial proof-of-concept work and prototype development for the technology was funded by a grant from UofL’s translational research program, which is part of the National Institutes of Health REACH network. The researchers also are products of entrepreneurial training and NSF’s (I-Corps) site translational research program, both at UofL.

By , the UofL team hopes to accelerate the technology’s path to market and explore other potential uses. While it’s initially being used for blood, this is a platform technology and could have multiple applications, including for storing or transforming other cell types.