Biomedical researchers at Texas A&M University report that they may have found a way to halt, or even reverse, the loss of cellular energy that comes with damage and aging. If future studies confirm the results, the discovery could lead to major changes in how many diseases are treated across medicine.
Dr. Akhilesh K. Gaharwar and Ph.D. student John Soukar, together with colleagues in the Department of Biomedical Engineering, have created a technique that supplies injured cells with fresh mitochondria. By replenishing these tiny energy producers, the method can restore energy output to previous levels and greatly improve the overall health of the cells.
Mitochondrial decline has been tied to aging, heart disease and several neurodegenerative conditions. A strategy that strengthens the body's natural capacity to replace worn-out mitochondria could, in principle, help address all of these problems at once.
As human cells grow older or are harmed by degenerative disorders such as Alzheimer's disease, or by exposure to harmful agents like chemotherapy drugs, their ability to generate energy steadily drops. A key reason is the shrinking number of mitochondria, the small, organ-like structures inside cells that supply most of the energy a cell uses. Whether in brain tissue, heart muscle or other organs, a decrease in mitochondria leads to weaker, less healthy cells that eventually can no longer perform their essential roles.
Nanoflowers Turn Stem Cells Into Mitochondria Donors
The research, published in Proceedings of the National Academy of Sciences, combined microscopic, flower-shaped particles called nanoflowers with stem cells. When stem cells were exposed to these nanoflowers, they began producing about twice as many mitochondria as usual. When the strengthened stem cells were then placed next to damaged or aging cells, they passed along their extra mitochondria to these neighboring, injured cells.
Once supplied with new mitochondria, the previously damaged cells were able to restore their energy production and normal activity. These revived cells not only showed improved energy levels but also became more resistant to cell death, even when they were later exposed to damaging treatments such as chemotherapy.
"We have trained healthy cells to share their spare batteries with weaker ones," said Gaharwar, a professor of biomedical engineering. "By increasing the number of mitochondria inside donor cells, we can help aging or damaged cells regain their vitality -- without any genetic modification or drugs."
Although cells are naturally capable of exchanging small amounts of mitochondria, the nanoflower-treated stem cells, which the team describes as mitochondrial bio factories, transferred two to four times more mitochondria than untreated stem cells.
"The several-fold increase in efficiency was more than we could have hoped for," said Soukar, lead author of the paper. "It's like giving an old electronic a new battery pack. Instead of tossing them out, we are plugging fully-charged batteries from healthy cells into diseased ones."
Making Mitochondria Therapies Last Longer
Researchers have tried other ways to increase the number of mitochondria inside cells, but these approaches often come with tradeoffs. Drug-based methods rely on small molecules that leave cells relatively quickly, so patients may need frequent and repeated treatments to maintain the effect. In contrast, the larger nanoparticles (which are roughly 100 nanometers in diameter) remain inside the cell and continue to stimulate mitochondria production more effectively. As a result, therapies based on this nanoflower technology might only need to be administered about once a month.
"This is an early but exciting step toward recharging aging tissues using their own biological machinery," Gaharwar said. "If we can safely boost this natural power-sharing system, it could one day help slow or even reverse some effects of cellular aging."
Molybdenum Disulfide Nanoparticles in Biomedical Use
The nanoflowers are made from molybdenum disulfide, an inorganic compound that can form many different two-dimensional shapes at very small scales. The Gaharwar Lab is among a small number of research groups investigating how molybdenum disulfide might be used for biomedical purposes.
Stem cells already play a central role in cutting-edge work on tissue repair and regeneration. Using nanoflowers to increase the performance of stem cells could mark an important step in making these cells even more effective in future therapies.
Versatile Approach for Many Tissues
One of the most promising aspects of the technique is its flexibility. Although the method is still in early stages and requires much more testing, it could theoretically be used to treat loss of function in many different tissues throughout the body.
"You could put the cells anywhere in the patient," Soukar said. "So for cardiomyopathy, you can treat cardiac cells directly -- putting the stem cells directly in or near the heart. If you have muscular dystrophy, you can inject them right into the muscle. It's pretty promising in terms of being able to be used for a whole wide variety of cases, and this is just kind of the start. We could work on this forever and find new things and new disease treatments every day."
The project received financial support from the National Institutes of Health, the Welch Foundation, the Department of Defense, and the Cancer Prevention and Research Institute of Texas. Additional backing came from the President's Excellence Fund at Texas A&M University and the Texas A&M Health Science Center Seedling Grant. Key collaborators included Texas A&M researchers Dr. Irtisha Singh, Dr. Vishal Gohil, and Dr. Feng Zhao.
