When muscles are damaged due to a lack of oxygen – ischemia – regenerating the muscles can be a challenge. Studies have been conducted to determine whether stem cell treatments could be provided to encourage the regrowth of damaged blood vessels in the muscles, but these treatments have not proven to be particularly effective in vivo.
Muscle ischemia occurs when blood is prevented from reaching muscle tissue, such as when there has been a traumatic injury to a limb or due to peripheral artery disease. Stem cells have potential to help treat muscle ischemia, not to replace damaged muscle cells but to encourage the growth of new blood vessels in damaged muscle tissue. Stem cells produce factors that encourage the formation of new blood vessels in the muscle and could help to restore the supply of oxygen and nutrients necessary for muscle regeneration.
Stem cells can be harvested from the adipose tissue of patients and can be injected directly into the site of injury in the muscle, but studies have shown the benefits to be short-lived. The ability of the stem cells to keep producing the factors necessary to stimulate blood vessel formation rapidly declines after injection.
Tumor necrosis factor (TNF) alpha is molecule produced in the body that has been shown to stimulate stem cells to secrete more of the required factors to stimulate blood vessel growth. It was hoped that incubating stem cells in TNF alpha before injection into patients would encourage the stem cells to secrete more of the necessary factors after injection, but again the results were only short-lived. Now, researchers at the University of Illinois at Urbana-Champaign have found a way to get the stem cells secreting the desired factors for much longer by using nanostimulators.
Nanostimulators are nanoparticles that have been seeded with TNF alpha which bind to the surface of the stem cells and deliver TNF alpha over an extended period after the stem cells have been injected into the site of injury.
“The primary benefit of stem cells toward tissue regeneration is not necessarily the ability for the cells to replace lost tissue, but to release beneficial growth factors and cytokines that assist in the process,” said study co-author Marni Boppart, a professor of kinesiology and community health at the University of Illinois. “The nanostimulators allow cells to release the beneficial factors longer than they would otherwise. This provides a significant advantage, particularly when cells are transplanted into injured, diseased or aged tissues.”
The new technique was tested in mice with surgically induced ischemia in a hind leg. The researchers isolated stem cells from adipose tissue, combined the stem cells with their nanostimulators, and injected them into the site of injury. After treatment, the researchers report that there was increased blood flow, oxygenation, and the mice were able to walk for longer as their legs became stronger.
The researchers report that their approach works better than chemical preconditioning of stem cells prior to injection. The stem cells exert their benefits for longer and the process is much faster as cells do not need to be cultured in TNF alpha prior to injection.
The researchers believe they can collect adipose tissue, isolate the stem cells, combine them with the nanostimulators, and inject them into patients in the same procedure and hope that their method could potentially be used to treat patients with long-term disabilities, such as those caused by periphery artery disease.
You can read more about the study in the paper – Surface Tethering of Inflammation-Modulatory Nanostimulators to Stem Cells for Ischemic Muscle Repair – which was recently published in the journal ACS Nano. DOI: 10.1021/acsnano.9b04926.