As we age, our bodies change and degenerate over time in a process called senescence. Stem cells, which have the unique ability to change into other cell types, also experience senescence, which presents an issue when trying to maintain cell cultures for therapeutic use.
While there are methods to remove older cells in a culture, the capture rate is low. Instead of removing older cells, preventing the cells from entering senescence in the first place is a better strategy, according to Ryan Miller, a postdoctoral fellow in the lab of Hyunjoon Kong.
“We produce biomolecules that are essential for therapeutics, so we want to keep the cell cultures healthy. In a clinical setting, the ideal way to prevent senescence would be to condition the environment that these stem cells are in, to control the oxidative state,” said Miller. “With antioxidants, you can pull the cells out of this senescent state and make them behave like a healthy stem cell.”
Current methods of antioxidant delivery have many shortcomings, including large variation in the amount of drug release over time and between cells.
The new method utilizes antioxidants in the form of polymer-stabilized crystals. Using microfluidics, a technology that allows researchers to work with incredibly small amounts of fluid, the researchers can create crystals that are all the same size and dosage, minimizing variation in drug release between cells. Furthermore, the crystals dissolve at a slower rate than traditional methods, making the release of the drug uniform over time, and increasing the duration of the drug’s effectiveness.
“When typical antioxidants are put into water or biological fluid, they lose their vital activity within six hours,” described Kong. “But the new antioxidant crystal remains bioactive for at least two days, so we can actually extend the duration of the drug, and also reduce the frequency with which we have to add antioxidants to the cell culture media. This minimizes the variation in the type of the biomolecules the stem cells are generating and improves the reproducibility of the product, which is one of the biggest challenges in biomanufacturing at the moment.”
Increased duration of the drug’s efficacy means that stem cell cultures can be kept out of the senescence state for longer, which leads to a larger harvest of the needed biomolecules for therapeutics.
“I think the beauty here is that this is a technology development paper, so this can be applied to various hydrophilic drugs, disease models, and methods applications,” said Han. “We’re showing that we can maintain a sustained release of this drug at a relatively constant rate for an extended period of time. There are a lot of exciting studies and directions that we can go with this technology.”
Ryan C. Miller, Jonghwi Lee, Young Jun Kim, Hee‐Sun Han, Hyunjoon Kong. In‐Drop Thermal Cycling of Microcrystal Assembly for Senescence Control (MASC) with Minimal Variation in Efficacy. Advanced Functional Materials, 2023; DOI: 10.1002/adfm.202302232
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign. “New drug delivery method can reverse senescence of stem cells.” ScienceDaily. ScienceDaily, 27 June 2023. <www.sciencedaily.com/releases/2023/06/230627191524.htm>.
Photo by Clement Falize