Recharging the powerhouse of the cell

(Press-News.org) Biomedical researchers at Texas A&M University may have discovered a way to stop or even reverse the decline of cellular energy production — a finding that could have revolutionary effects across medicine.

Dr. Akhilesh K. Gaharwar and Ph.D. student John Soukar, along with their fellow researchers from the Department of Biomedical Engineering, have developed a new method to give damaged cells new mitochondria, returning energy output to its previous levels and dramatically increasing cell health.

Mitochondrial decline is linked to aging, heart disease and neurodegenerative disorders. Enhancing the body's natural ability to replace worn-out mitochondria could fight all of them.

As human cells age or are injured by degenerative disorders like Alzheimer's or exposure to damaging substances like chemotherapy drugs, they begin to lose their ability to produce energy. The culprit is a decrease in the number of mitochondria — small, organ-like structures within cells responsible for producing most of the energy cells use. From brain cells to muscle cells, as the number of mitochondria drops, so does the health of the cells, until they can no longer carry out their functions.

The study, published in Proceedings of the National Academy of Sciences, used a combination of microscopic flower-shaped particles — called nanoflowers — and stem cells. In the presence of these nanoflowers, the stem cells produced twice the normal amount of mitochondria. When these boosted stem cells were placed near damaged or aging cells, they transferred their surplus mitochondria to their injured neighbors.

With new mitochondria, the previously damaged cells regained energy production and function. The rejuvenated cells showed restored energy levels and resisted cell death, even after exposure to damaging agents such as chemotherapy drugs.

"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."

While cells naturally exchange some mitochondria, the nanoflower-boosted stem cells — nicknamed mitochondrial bio factories — transferred two to four times more mitochondria than untreated ones.

"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."

Other methods of boosting the number of mitochondria in cells exist, but have significant drawbacks. Medications require frequent, repeated doses because they are composed of smaller molecules that are quickly eliminated from cells. The larger nanoparticles (which are roughly 100 nanometers in diameter) remain in the cell and continue promoting the creation of mitochondria to a greater extent. This means therapies created from the technology could potentially only require monthly administration.

"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."

The nanoparticles themselves are made of molybdenum disulfide, an inorganic compound capable of holding many possible two-dimensional forms at a microscopic scale. The Gaharwar Lab is one of the few groups to explore molybdenum disulfide’s biomedical applications.

The therapeutic potential of stem cells has been a hotbed of cutting-edge research in tissue regeneration. Using nanoflowers to boost stem cells could be the next step in making these cells even better at what they do.

One of the major benefits is the method’s potential versatility. While the approach has yet to be fully explored, it could, in principle, treat loss of function in tissues across 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 research received funding from the National Institutes of Health, the Welch Foundation, the Department of Defense, and the Cancer Prevention and Research Institute of Texas. Additional support was provided by the President's Excellence Fund at Texas A&M University and the Texas A&M Health Science Center Seedling Grant. Other key collaborators in this study include Texas A&M researchers Dr. Irtisha Singh, Dr. Vishal Gohil, and Dr. Feng Zhao. 

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