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Stem Cells Provide Greater Insight Into Rotator Cuff Disease.

ANN ARBOR, February 26, 2019 -- New animal research explores stem cells in the rotator cuff in hopes of understanding why fatty accumulation happens at the tear site, instead of proper muscle healing.

Rotator cuff tears are common injuries, and proper healing of the shoulder muscle is often difficult.

"Chronic tears often result in fat accumulation within the rotator cuff muscles, resulting in negative clinical outcomes, including weakening and atrophy of the muscles," said Manuel Schubert of Michigan Medicine. "It's believed that this process of fat infiltration makes rotator cuff muscle damage one of the most difficult to rehabilitate after injury."

Schubert said that the process of fat accumulation following a tear appears to occur more frequently in rotator cuff muscles than other muscle groups.

But why this particular muscle set?

"We wanted to determine if there are cellular, molecular and genetic reasons for why rotator cuff muscles tend to develop this fat accumulation after injury," he said.

In a new study, Schubert and team used a mouse model to isolate specific stem cells, called satellite cells, in rotator cuff muscles, as well as calf muscles for comparison, to determine the extent of muscle and fat cells that develop from these satellite cells.

They then performed DNA-level studies to understand how the gene pathways of the muscles may differ.

"Even though the stem cells obtained from the rotator cuff muscles and the calf are thought to be the same kind of muscle stem cells, we wanted to determine if these cells are different in how their development is controlled," Schubert said, "Which may provide insight for why fat tends to accumulate more in rotator cuff muscles."

The research team first obtained and isolated stem cells in each muscle to identify which cells develop into muscle cells and which develop into fat cells.

The muscle stem cells from the rotator cuff developed into 23 percent fewer muscle cells and they showed an 87 percent decrease in a marker for muscle formation compared to the calf muscle stem cells. The rotator cuff stem cells also had a four- to 65-fold increase in markers of genes involved in fat cell generation.

They then performed DNA-level studies in the stem cells from each muscle to examine gene activation.

The studies identified 355 different regions of DNA between the stem cells from the rotator cuff and the calf muscle. Using a pathway enrichment analysis they found that the genes activated in the rotator cuff muscle were in regions related to fat metabolism and adipogenesis, or the formation of fat or fatty tissue.

The activation of these regions suggests that the muscle stem cells from the rotator cuff have DNA that is programmed to more easily become fat cells.

"This study was the first of its kind to study DNA modification in the context of rotator cuff disease," said Christopher Mendias of Michigan Medicine. "It allowed us to gain insight into studying the nature of this common and debilitating condition, and it will set the stage for many additional studies."

While further research is needed, this study provides insights into how future research in the rotator cuff could potentially lead to new therapeutic and clinical treatments.

On the therapeutic side, for example, it may be possible in the future to take a patient's own muscle stem cells from a muscle that heals better and with less fat formation than the rotator cuff muscles. During surgery, physicians could then transplant these stem cells from a muscle, such as the calf, to rotator cuff muscles and perhaps they could help the muscle heal with less fatty infiltration.

The researchers plans to continue examining the rotator cuff. They have research underway to further study the nature of fat accumulation in patients with rotator cuff tears and understand how stem cells and immune cells work together to modify the muscle after injury.

Citation: Manuel F. Schubert et al., Reduced Myogenic and Increased Adipogenic Differentiation Capacity of Rotator Cuff Muscle Stem Cells. The Journal of Bone and Joint Surgery, 2019; 101 (3): 228 DOI: 10.2106/JBJS.18.00509


Contact: C.L. Mendias,
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Title Annotation:Basic Research
Publication:Stem Cell Research News
Date:Mar 11, 2019
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