There is a lot of discussion about why StemWave is referred to as the “stem cell machine”.  StemWave and SoftWave are amazing technological advancements that been allowed for use by the FDA for pain and inflammation reduction and more.  However, do the electrohydraulic shockwaves produced by StemWave and SoftWave influence stem cell function to aid in regenerating tissue?  It’s not enough to simply say it does.  As doctors, we owe it to our patients to understand and educate how to best understand how this technology works.

A StemWave Electrode

First, we need to understand that the shockwaves produced by the StemWave and SoftWave devices are mechanical stimulation.  The electrohydraulic shockwave is produced by a very strong electrical discharge in water.  Using an electrode of highly conductive metal, electricity is passed between the two poles (plus and minus).  This superheats the surrounding water (several thousand degrees Celsius) and creates a plasma bubble.  This process is similar to how a spark plug works in an internal combustion vehicle.  The plasma bubble then implodes, creating a radial wave, then explodes.  This is the actual shockwave.

The power of the shockwave is considerable, and it must be directed by an applicator head. StemWave uses a focused applicator head while SoftWave uses an unfocused one.   The initiated shockwave creates energy of high positive pressure that peaks around 100 MPa over an extremely short period of time (10^-9 seconds).  The energy then drops off quickly and creates a low-pressure phase of tensile stress of 10 MPa (allowing the cell to expand and conceivably stretch).  The 10 MPa tensile stress is sometimes considered to be a ‘negative’ stress.

The true shockwave essentially compresses, then stretches, the cell.  The speed of the entire process is very fast.  The plasma bubbles are so small that they do not create any recognizable heat.  We also have to recognize that the shockwaves absorb differently based upon what tissues they are directed at as each type of tissue offers different impedance levels.

The mechanical input delivered by the shockwave is registered in our tissues and the body adapts in a biological/chemical way.  This is called Mechanotransduction.  Simply put, the mechanical stimulation from shockwaves creates biochemical changes in the target tissue.  There are many biochemical changes that occur, but there are two main ones we consider.  One, upregulation of immune function and two, receptor activity that stimulates stem cell function.  Although scientists are able to see the changes from ESWT, they cannot fully yet understand why certain reactions are occurring.  It’s a fascinating and growing science.

What is understood is that nothing works like ESWT, and the results are unmatched.  The International Society of Shock Wave Therapy makes many claims about shock wave therapy, and they follow the research very closely.  After all, it is the body responsible for how the world views shockwave therapies from all companies.  It is great to have an international body of scientists working to validate all the amazing things ESWT is used for now, and what it will be used for in the future.  We are hopeful that ESWT can be used to regenerate many tissues, cartilage being one of extreme importance.  This research is certainly on its way.

Now let’s cover the topic of tissue regeneration through stem cell activation…

Tissue regeneration requires stem cell activation and differentiation.

When we have an injury, be it a macro (big) trauma, or micro (small) trauma, our tissues have to be able to communicate with the rest of our body to inform it of the harm.  This is done by damaged cells releasing different constituents.  Some of these include chromatin (affects DNA health), proteins, and RNA (it forms stable double helix RNA when released in this fashion). In some spaces it is also called cytoplasmic/cytosolic, or even messenger RNA.

Researchers have given a name to the group of released chemicals and that is Damage/Danger Associated Molecular Patterns (DAMPs).  DAMPs create inflammatory processes and can even play a role in disease formation due to the inflammation they create.

What is interesting about this grouping of chemicals is that it is currently believed that RNA is responsible for the heavy recruitment of the healing agents.  This is discussed below with research to validate this point.  The body responds to injury by activating the innate immune system.  Doing so creates new blood supply to the treated area, called angiogenesis.  This is how stem cells are recruited to the areas of treatment.  They are brought in through the new blood supply.  Stem cells are used to rebuild/repair the damaged tissues.  The receptors that are responsible for this process are called toll-like receptors (TLR).  The most involved and studied are the TLR2, TLR 3, TLR4, and TLR5.  The human body has 10 TLRs but there is a bit of a debate to this.  The ones that most apply to our discussion about reduction of inflammation and regeneration are the TLR3 and TL4.

With tissue healing and regeneration, we can look at the body as almost having two receptor effects.  One is a  ‘good guy at the end’ and the other, ‘I try to be a good guy, but all too often am a bad guy’.  TLR3 is the good guy at the end and TLR4 is sometimes the bad guy!   TLR4 can be useful as it brings about inflammation to help with fighting off bacterial infection.  However, it tends to create a lot of issues by bringing about excessive inflammation that can exacerbate existent issues or create its own problems.  In an ideal situation, TLR3 and TLR4 work together.  However, with lots of inflammation, sometimes their communication isn’t as it should be and this can lead to excessive damage.

We may want to consider this the case with over-swelling of an ankle injury that leads to compartment syndrome.  Another example is too much swelling in the brain after a head injury.  Many excessively inflamed conditions may be due to the TLR4 response.  For example, studies show that TLR4 can create vasospasm, neurodegeneration, CNS inflammation, and a host of other bad effects.  Its deleterious effects on neuroimmune and neuroendocrine function can be quite scary.  Although TLR4 likely thinks that it is trying to help, at times, it’s best to not invite TLR4 to the area we want to heal.

On the other hand, TLR3 ultimately brings about a cell protective effect.  It is also responsible for angiogenesis (new blood vessels).  This is a result of the Mechanotransduction, previously discussed, whereby the shockwave (mechanical input) creates a biological response to create new vessels (biochemical effect).  The entire mechanism of how this occurs is still not entirely understood, but it is known to occur.  TLR3 also triggers what we’d consider to be a more proper immune response and aids in delivering stem cells to help regenerate.  Although TLR3 is known to trigger an early inflammatory response, it has a potent anti-inflammatory effect following.

We should keep this in mind when we are administering shockwaves as too many and too much intensity might actually not work in the patient’s favor.  So, why the good guy and bad guy scenario?  Well, what we know is that TLR3 and TLR4 communicate.  Ideally, the communication between the two helps to bring out the best innate treatment effects.  However, this is not always the case.  Is it possible that true ESWT can actually help the body heal better than it can on its own?

Let’s take a half step backward and regroup.  Where do StemWave and SoftWave come in with all of this?  What if I were to tell you that ESWT has been shown to not only help bone and tendons heal, but also increase blood flow in muscles?  Can shockwave therapy help prevent arthritis?  Can it help with damaged cartilage, bone disease, motor function, can it regenerate muscles, and more? How about aiding organ tissue?  Well, there are studies that show it does just about all of this.

But how?  (Think Mechanotransduction!)

The ‘how’ is based on what shockwaves do to the cell that mimic what an injury does.  Let’s now apply that mechanical stimulation creating the biochemical effects we read about earlier (Mechanotransduction).  We learned above that injured cells leak certain constituents (DAMPs).  This leads to the TLR response (called Pattern Recognition Receptors).  Electrohydraulic shockwaves, moving at over 1500 m/s, first compress, then stretch, the cell.  Although they do NOT create damage of any kind or create heat, they trick the cell into thinking something is wrong.

This shockwave effect stimulates the cells to release those same constituents that damaged cells leak, and as you can guess now, the TLR respond.  It is important to note that TLR3 is not tricked by just any compound coming out of a cell.  TLR3 is only triggered by RNA.  This is where electrohydraulic shockwave therapy gets even more amazing.  shockwaves imitate an injury scenario without actually creating any injury. They are effective at downregulating (reducing) the effects of TLR4 (remember, the TLR that tends to be seen to be more of a bad guy than a good guy), while enhancing the effects of TLR3 (initial inflammation followed by an anti-inflammatory effect…the good guy).  This is quite convenient and amazing for regeneration!

Conclusion/Cliff Notes:  Directly stated, StemWave and SoftWave electrohydraulic low-medium energy shock waves affect the tissues/cells in such a way that mimic injury without actually creating trauma of any kind.  The tissues/cells release certain constituents (the most important being RNA) that trigger the body’s innate healing system to take notice.  A true injury will elicit a response from TLR3 and TLR4.  But, true electrohydraulic shockwaves reduce the activity of TLR4 while increasing the effective function of the TLR3.  By doing so, we activate a high level of healing and regeneration.

I hope this blog provides a good amount of information to help you better understand exactly how StemWave and SoftWave ESWT work.  This blog will be tweaked and updated as new research becomes available.

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