Rotator Cuff Stem Cells More Likely to Become Fat than Muscle?

barbara

Pioneer Founding member
Regenexx Blog
3-11-19
Dr. Chris Centeno

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Some patients with rotator cuff tears have a problem that most don’t know exists. Their rotator cuff muscle begins to atrophy and when this happens, surgical repairs are less likely to be successful. So what causes this issue is a big deal. Now new research shows that the problem may lie more in the cells that make up the rotator cuff. Let me explain.

Understanding Rotator Cuff Tears
The rotator cuff is made up of a variety of muscle and tendon subparts that form into a single muscle unit in the shoulder. The shallow ball-and-socket shoulder joint has the greatest range of motion of any joint in the body, and a healthy rotator cuff supports all of the joint’s complex motions and keeps the entire structure nice and stable.

As with most muscles, the rotator cuff can become injured when the shoulder is overstressed. For example, when lifting a heavier load overhead than the muscle can comfortably support, the rotator cuff can tear. Tears, however, aren’t just the result of overloading the joint; they also happen as we age due to normal wear and tear. It’s important to understand that normal-wear rotator cuff tears may or may not result in shoulder pain, so when these are found on MRI, it shouldn’t be assumed that they are the cause of the pain.

Why the Rotator Cuff Isn’t the Best Self-Healer
It’s well known that the rotator cuff isn’t very good at healing itself. First, we know that as we age, the blood supply to the rotator cuff lessens. Second, I also shared a study that found that there may be fewer stem cells in the shoulder area when there are rotator cuff tears. What does this mean exactly? Our stem cells are the body’s repair cells, and when an area is stem-cell deficient, it can’t properly repair those small injuries that occur over time. In the shoulder, this failure to heal the small things may eventually lead to rotator cuff tears with aging.

Finally, there may also be a genetic connection to why the rotator cuff isn’t a very good self-healer. Another study found that specific gene expressions in rotator cuff tear patients were responsible for cells making proteins that would then break down tissue and not for making new tendon cells that would be necessary for helping to heal the tear. In any of these cases, add rotator cuff surgery to the mix, and it makes sense that operating on this already weakened tissue that has limited ability to self-heal may make things worse.

Now, there’s a new study that expands more on the rotator cuff and what really happens with those stem cells when repair is needed.

Rotator Cuff Stem Cells May Be More Likely to Become Fat than Muscle
The new study compared stem cell differentiation in both the rotator cuff muscle in the shoulder and the gastrocnemius muscle in the leg. In this animal model, they used the resident muscle stem cell known as a satellite cell. Stem cells affect healing by moving into the damaged area and typically differentiating into, or becoming, the specialized cell type necessary to repair the tissue (for further explanation on differentiation, watch my brief video to the right).

How do stem cells work? Differentiation or the Cellular Oedipus Complex
The results in this case? The rotator cuff satellite cells differentiated into 23% fewer muscle cells than those from the gastrocnemius. In addition, there was a four-fold increase in adipogenesis (fat production) by the rotator cuff satellite cells.
In addition, researchers also found hundreds of differences in gene expression in the two muscles with the rotator cuff showing heavy expressions in those involved in lipid metabolism and adipogenesis, causing them to suggest both cellular and gene expression links to the adipogenesis in the rotator cuff. They also suggested transplanting satellite cells from other muscles into the rotator cuff to improve the chances of muscle tissue rather than fat.

Getting the Right Stem Cells to the Rotator Cuff
This study may explain why fat atrophy (those fatty deposits that cause muscle weakness) is a problem associated with poor rotator cuff surgery outcomes; as the body attempts to self-heal, those rotator cuff stem cells may differentiate into fat cells rather than muscle cells. So how do we get the right kind of stem cells to the rotator cuff to facilitate healing?

One way to do this may be focusing on the bone marrow cells. One of those cell types, hematopoietic stem cells, are found in muscles of animals that are excessively exercised. This and other studies (study 1, study 2) has lead researchers to conclude that bone marrow stem cells participate in natural mechanisms of muscle repair. Hence, does it makes sense to directly inject these cells into these damaged muscles? One easy way of doing that would be injecting bone marrow concentrate into torn rotator cuff muscles. However, does this help real patients? For example, one recent study concluded that performing a rotator cuff repair and then injecting bone marrow stem cells during the surgery reduced re-tear rates.

Do you always need the surgery? In our experience and based on what we are finding in our own rotator cuff tear randomized controlled trial (RCT), in select patients, most of these same results can be had by skipping the surgery. In these cases, we replenish bone marrow stem cells through precise injections. Learn more about this RCT by watching my video below:

The upshot? This problem with rotator cuff muscle stem cells wanting to become fat may be the reason why we see fat atrophy in this injured structure. In the meantime, we now have research that suggests that adding in bone marrow stem cells to the tear, which can replace the function of muscle satellite cells, is likely a good idea to promote healing.
 
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