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3D imaging reveals new potential targets for treating muscle disease and injury

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A new form of 3D imaging of muscles could lead to new treatments for muscle diseases and injuries, according to a study published in the Journal of Physiology.

A research team at the University of California, San Diego and the Rehabilitation Institute of Chicago (RIC) led by Dr Richard Lieber, chief scientific officer at RIC, used 3D imaging to “see” inside muscle and trace long cables made up of collagen.

These collagen cables are one culprit behind muscular diseases and injuries, so targeting them could provide treatments, the researchers said.

According to the Physiological Society, eight million people in the UK suffer from muscular diseases and injuries including muscular dystrophy, cerebral palsy, exercise-related injuries, rotator cuff tears, and age-related muscle loss.

All of these conditions can result in stiff, dysfunctional muscles due to changes called fibrosis — a thickening and scarring of connective tissue. The Physiological Society described fibrosis as “a roadblock to muscle recovery” which can result in muscle pain, weakness and limited range of motion, and may require surgery.

In the study, the researchers used a mouse model of skeletal muscle fibrosis to investigate the structure and function of collagen. They visualised collagen with conventional 2D and a newly developed method of 3D electron microscopy, mechanically measured muscle stiffness, and quantified the collagen producing cells.

The results were surprising because the collagen structures did not fit the textbook definition of muscle, explained Dr Allison Gillies, first author of the study.

Collagen had not been previously known to form long chains in muscle. Researchers had seen collagen outside muscle cells, but had not determined the level of organisation that could only be visualised by 3D microscopy.

The study showed that, when muscles become fibrotic, the number of cables and cells that produce collagen both increase. These collagen cables and the cells that produce collagen are two potential targets for treating muscle disease and injury.

“Reducing the amount of collagen cables or collagen producing cells in fibrotic muscle may improve muscle function and reduce pain, even obviating the need for corrective surgery,” Dr Lieber said.