CTSI Pilot Program: Improving mitochondrial function to help patients with osteoporosis

Sometimes, as Albert Einstein once famously opined, scientific breakthroughs come from looking at an old problem from a new angle.

“In the cardiovascular field, it’s all about mitochondria, and most of the cardiovascular literature has been about protecting mitochondrial function and boosting it during aging,” said Roman Eliseev, M.D., Ph.D., assistant professor of orthopaedics. “But very little has really been studied about the role of mitochondria in bone biology.”

Roman Eliseev, M.D., Ph.D.

Roman Eliseev, M.D., Ph.D.

Now, Eliseev thinks that techniques being applied to aging patients with cardiovascular disease might also apply to aging patients with osteoporosis.

His research, supported by a 1-year Pilot Grant from the CTSI, began on July 1.

For several years, researchers have been studying mesenchymal stem cells that can transform into other cells, such as bone, cartilage, muscle or fat, when necessary. These cells are also responsible for bone repair.

But if the energy-producing mitochondria within those cells lose their effectiveness, then the cell won’t have the energy to differentiate into the various cells the body needs. This energy loss often occurs in aging patients, putting them at higher risk for various degenerative diseases.

Eliseev has seen this disruption occur in the bones of aging mice and believes that the same disruption likely occurs in humans.

“People with osteoporosis have an increased risk of fracture, and when it occurs, the fracture doesn’t heal well. It can take months,” said Eliseev. “But by boosting mitochondrial function in mesenchymal stem cells, maybe we can accelerate that fracture healing in aged osteoporotic individuals.”

Eddie Schwarz, Ph.D., who was on the committee that selected Eliseev’s project from a variety of Pilot proposals, said that the project’s originality — and the fact that Eliseev is one of the only researchers studying the topic — were among the reasons that it was chosen for a CTSI Pilot Grant.

“It ties together a triad of basic sciences — metabolomics, stem cells, and osteoporosis,” said Schwarz, associate director for funding programs at the CTSI. “It was the basic science connection of these things that enabled it to do very well.”

With data generated from the Pilot study, Eliseev is hoping to seek an R01 grant to further illustrate the role of the mitochondria in mesenchymal stem cells, and run a small clinical trial in humans.

Eliseev’s findings may be quickly translatable to human care, as several drugs that protect mitochondrial function are already in clinical trials and could be repurposed for the necessary treatments. Bone marrow biopsies could also be used to extract mesenchymal stem cells from a patient, which could then be manipulated them to enhance mitochondrial function, and reinserted into the patient to accelerate fracture healing.

The CTSI recently released requests for applications for both the CTSI Incubator Program and the CTSI Pilot Awards Program.

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