Aging leads to changes and deterioration in our bodies, a process known as senescence. Even stem cells, which have the remarkable ability to transform into different cell types, experience senescence. This poses a challenge when maintaining cell cultures for therapeutic purposes because once the cells enter a senescent state, they stop producing vital biomolecules and may even produce substances that counteract therapeutic treatments.
To address this issue, Ryan Miller, a postdoctoral fellow in the lab of Professor Hyunjoon Kong, proposed a different approach. The team works with mesenchymal stem cells derived from fat tissue, which produce essential biomolecules for therapeutics. Their goal is to keep these cell cultures healthy by preventing senescence. They discovered that by conditioning the environment with antioxidants, they could pull the cells out of the senescent state and restore their healthy behavior.
Although antioxidants can delay senescence, the current methods of delivering antioxidants have limitations, such as inconsistent drug release over time and between cells. However, a recent study published by the labs of Kong and Assistant Professor Hee-Sun Han describes a novel and reliable method of delivering antioxidants to stem cells. The study, with Miller as the first author, was published in Advanced Functional Materials.
The new method involves using antioxidants in the form of polymer-stabilized crystals. Instead of growing crystals in reactors, the researchers utilized microfluidics, a technology that allows them to work with minute amounts of fluid. This enabled them to create crystals of uniform size and dosage, minimizing variation in drug release between cells. Moreover, these crystals dissolve at a slower rate compared to traditional methods, resulting in a uniform and extended release of the drug, thus increasing its effectiveness and duration.
Maintaining a narrow variation in the drug’s release profile is crucial, as it helps to achieve optimal concentrations needed for therapeutic outcomes. Antioxidants dissolved in water experience a bursting period where a large amount dissolves quickly and then declines rapidly. In contrast, the crystal-based delivery system ensures a sustained and controlled release, which aids in maintaining the desired concentration range.
Typical antioxidants lose their effectiveness within six hours when added to water or biological fluids. However, the new antioxidant crystal remains bioactive for at least two days, extending the drug’s duration and reducing the frequency of antioxidant supplementation in cell culture media. This minimizes the variation in biomolecule production by stem cells and improves the reproducibility of the therapeutic product—a significant challenge in biomanufacturing.
The increased duration of the drug’s efficacy allows stem cell cultures to remain in a non-senescent state for longer, resulting in a larger yield of the necessary biomolecules for therapeutics. Additionally, this method could be employed in patient-derived stem cell treatments, where the patient’s own biomolecules are used to address tissue ailments or diseases.
When biomolecules from donors are used instead of the patient’s own cells, there can be adverse effects. Ideally, stem cells harvested from the patient could be grown in a bioreactor, and the biomolecules produced could be utilized for therapeutic purposes. However, elderly patients tend to have a higher population of senescent cells that do not secrete the required biomolecules. By reverting these cells to a healthy state, a larger quantity of therapeutically relevant biomolecules can be obtained for the patient.
The team aims to further refine the biomanufacturing process, but they see numerous potential applications for their methodology beyond antioxidant delivery to stem cell cultures. Since most cells experience senescence, this technique could be applied to other cell cultures used in medicine and therapeutics. Additionally, the crystals could serve as a vehicle for sustained and controlled delivery of antioxidants or other drugs directly to the target tissues of patients.
This technology development holds great promise for various hydrophilic drugs, disease models, and future applications. The researchers believe that their approach can be adapted and applied to different drugs, disease models, and therapeutic methods. By maintaining a sustained release of drugs at a constant rate over an extended period of time, the crystal-based delivery system offers exciting possibilities.
One potential direction is the controlled and prolonged delivery of other hydrophilic drugs. The crystals can be used to encapsulate different types of drugs, allowing for sustained release and consistent drug concentrations. This has the potential to improve the efficacy and reduce the frequency of drug administration, enhancing patient convenience and compliance.
Moreover, the technique could find applications beyond stem cell cultures. Since senescence affects most cell types, the crystal-based delivery system could be employed in other cell cultures used in medicine and therapeutics. By controlling senescence and optimizing biomolecule production, this approach may revolutionize biomanufacturing processes and improve the reproducibility of therapeutic products.
Additionally, the crystals can be used to deliver antioxidants or other drugs directly to target tissues in patients. By designing crystals with specific properties, such as size and dissolution rate, tailored drug delivery to specific tissues or organs can be achieved. This targeted approach may enhance the effectiveness of treatments while minimizing side effects associated with systemic drug administration.