We have recently obtained another key weapon in our
office. This weapon is a true Class 4 COLD LASER. But this is not like the
typical class 4 laser. Many people know about lasers but are not exactly sure
how they achieve their goals. The basic science of lasers is that they use the
principle of Photobiomodulation. The following illustration shows this concept.
Photobiomodulation is defined as a form of
light therapy that utilizes non-ionizing light sources. These include near ultraviolet, visible light, infrared, microwave, radio waves,
and low-frequency radio frequency (long-wave) are all examples of non-ionizing radiation. By contrast, far
ultraviolet light, X-rays, gamma-rays, and all particle radiation from
radioactive decay are ionizing
light sources. Photobiomodulation is a NON-THERMAL process involving endogenous
chromophores. The first law of photobiology
explains that for a low power visible light to have any effect on a living
biological system, the photons must be absorbed by electronic absorption bands
belonging to some molecular photo-acceptors, which are called chromophores.
Here is a good explanation of chromophores.
A chromophore is the part of a molecule
responsible for its color. The color that is seen by our eyes is the one not
absorbed by the reflecting object within a certain wavelength spectrum of
visible light hence the objects steal the objects from the wheel. Chromophores will elicit reactions at various biological sites. This process
results in beneficial therapeutic outcomes including but not limited to the
alleviation of pain or inflammation, immunomodulation, and promotion of wound
healing and tissue regeneration. We can see this principle in
the following illustration:
What we are able to see is that a very
important aspect of laser therapy involves the mitochondria. The mitochondria
produce ATP which is the body's energy currency. It does this by stimulating
the Cytochrome C Oxidase which is an enzyme in the electron transport chain of
the Krebs cycle. Laser therapy produces a
shift in overall cell redox potential in the direction of greater oxidation and increased Reactive Oxygen Species
(ROS) generation. In a biological
context, ROS are formed as a natural byproduct of the normal aerobic metabolism
of oxygen and have important roles in cell signaling and homeostasis. ROS are well known to stimulate
cellular proliferation of low levels, but inhibit proliferation and kill cells
at high levels. Nitric oxide is also involved in laser therapy. It may be
photo-released from its binding sites in the respiratory chain and elsewhere.
Nitric oxide will increase vasodilation and thus increasing blood supply.
Nitric oxide may also act as a neurotransmitter helping with pain control. Also,
not to be overlooked is the fact that the mitochondria have many important
tasks in many other aspects of cell biology and cell signaling pathways.
It has been proposed that
the redox state of a cell regulates cellular signaling pathways that control
gene expression. Modulation of the cellular redox state can activate or inhibit
signaling pathways. When we start affecting the various pathways and affecting
gene expression we have now crossed into the field of Epigenetics. Several
regulation pathways are mediated through the cellular redox state. Changes in
redox state induce the activation of numerous intracellular signaling pathways,
such as nucleic acid synthesis, protein synthesis, enzyme activation and cell
When all is said and done the application of a
therapeutic dose of light to impaired or dysfunctional
tissue leads to a cellular response mediated by mitochondrial mechanisms that
reduce pain and inflammation, speed healing, and cell hemostasis. These cellular mechanisms responsible for the effect of
visible light on cells include cytochrome c oxidase. Mitochondria are thought
to be a likely site for the initial effects of light, leading to increased ATP
production, modulation of reactive oxygen species, induction of transcription
factors, and possible changes in mitochondrial DNA. These effects in turn lead
to increased cell proliferation and migration particularly by fibroblasts.
Fibroblasts are responsible for the production of collagen which is a basic
building block for many of the bodys tissues including bone, cartilage etc. The
lasers overall effect is that it will
bio stimulate cells to increase cellular growth and regenerative activity,
while simultaneously deactivating 7 or the 9 enzymes that cause inflammation by
up to 70%.
Another unique aspect of lasers is that they are considered to be monochromatic,
coherent and collimated. Monochromatic means that there is a single wavelength
which stimulates particular human tissues that will only respond to that
specific wavelength being utilized. Coherent means that it minimizes the photon
scatter as light interacts with the tissue. Lastly, because lasers have a
higher power that works with a specific wavelength, they are collimated which
allows it to actually reach the deep tissues. The following illustration drives
home these points.
ARE LASERS CLASSIFIED?
One may ask how are the lasers classified? The FDA classifies lasers from I to IV. For instance, a Class IV Laser is any laser
device that the FDA has determined is powerful enough to pose a significant
risk of injury to the eye. Consequently, being Class IV does not necessarily
laser more effective, as that would depend upon
what you intend to do with it and how you use it. Some Class IV lasers are used
in health and medical settings for a wide range of therapeutic applications.
Others are used for construction, cutting, burning and by hobbyists such as
high-powered laser pointers.
Let us look at some further
perimeters of the Class IV Lasers. Hot lasers are known as Class IV lasers. Class IV lasers
have a power output above 500 milliwatts (mW). At a lower power range, hot
lasers are used for therapeutic purposes. Class IV lasers can cut tissue during
surgical procedures. Most Class IV lasers are called hot lasers because they
can rapidly increase tissue temperatures. The one common tread with class IV
lasers is that they have higher power outputs and most translate the energy to
On the other hand, most, cold lasers are also known
as low-level lasers, they are among Class II and Class III lasers. Cold lasers
have a power output of less than 500 mW. These lasers are called cold because
they do not generate a thermal effect. But we must realize that the decreased
power will also decrease the penetration depth of the laser. The vast majority
of lasers in medical use are not true class IV cold lasers but class III
lasers. Many of them are advertised as a Class IV lasers but in reality, they
are Class III lasers. If they happen to a Class IV laser then most of the
energy is expended as heat. They may have some bells and whistles and other
gimmicks. But it does not make them any more effective. As we can see in the
following illustration, typically a Class IV laser will need much less
treatment time than a Class III laser. Also, we will obtain a much greater
depth of penetration with the Class IV laser. What most medical professionals
do not seem to understand is that a laser with many medical benefits produces
it benefits with LIGHT ENERGY NOT HEAT. Thus, when one is looking to
derive benefits from the laser, heat should not be a consideration. THE
PHOTONIC ENERGY IS WHAT ONE NEEDS TO BE CONCERNED ABOUT. The following
illustration will give an idea about the difference. The most significant
difference in the various types of lasers is the depth of penetration.
There is a misunderstanding
that a more efficient laser will produce heat.
This is simply not the case. Most of the time when we are utilizing a laser we
are interested in the depth of penetration. We also do not wish to subject the
patient to long hours of treatment. So, if we can eliminate the heat and get
penetration of depth than we may have something special. When all is said and
done IT IS THE PHOTONIC ENERGY WHICH ACCOMPLISHES THE REPAIR.
WHAT WOULD BE MY CHOICE FOR AN OPTIMAL LASER?
I have used lasers for many years. The use of lasers
for musculoskeletal conditions has long passed the point of being experimental.
There are many different types of lasers in use. In our clinic we have been
very happy with our laser sleeves and our original hand-held Class IV type
laser. The original Class IV laser which we have been using requires eyewear
protection and it will produce heat which could burn the skin. Nevertheless, it
was efficient but at the same time there was a risk of thermal injury and
because of the thermal considerations I believe the penetration was limited.
If I were able to design a laser I would want one to
be a Class IV laser that essentially did not cause any thermal damage. To be
effective, the laser would have to have a power output of greater than 500
milliwatts. It would need to be monochromatic and have a wavelength of
approximately 680 mM which is the ideal wavelength to stimulate the
mitochondria. This is the sweet spot in the red spectrum range.
It obviously requires eyewear. Also, it is cold laser. What are the differences
between and hot and cold laser? Again, Cold Lasers are therapeutic
lasers that produce an insignificant amount of heat and are extremely safe for
use by professionals.
us take a look at the specs of the new laser. The output of the new laser is
750 milliwatts. Remember, the energy output for the Class IV laser is above 500
milliwatts. So, we definitely classify as a Class IV laser by power output. The
new laser is monochromatic so it essentially stays on one wavelength and its
wavelength is 680 nM which is the sweet spot for mitochondrial stimulation etc. The
wavelength is 680 nm. This is the sweet spot in the red spectrum range. This
provides both a large safety margin and potent force. If
we were to lower the wavelength we could lower the safety margin. The last
aspect to an ideal laser is what is called lumen intensity. We need to look at
some physical aspects of light when looking at lumen intensity. There are three
terms we want to know when assessing lumen intensity. These are lumens, lux and
candela. A good way to remember the differences
between terms is:
are how much light is given off
how bright your surface will be
measures the visible intensity from the light source.
The lumen intensity of the new laser is 550 lumens per millimeter
of tissue radiated. The beam profile is one millimeter. This last spec will
allow the user to pinpoint targeting tissue. Example would be a meniscus tear
located posteriorly in the medial compartment, or a tear in the supraspinatus
located inferior to the acromion for example. This later spec you can only
utilize the function of when the laser is a true class four. You need the power
of penetration without the heat damaging aspect. This is a very important aspect
and the one important principle which needs to be conveyed and understood - not
easy to do! True photonic intervention is dependent on absorption of the light
force or energy. Not in the heat transmission normally incorporated into laser
modules. The light is the energy! Again, we see a picture of our new Class IV
laser. Notice it is a hand-held laser. It is battery powered. Many times,
simplicity is a goal strived for but many times seldom achieved.
The next illustration is a summation of all the
benefits our new Class IV laser is able to achieve while at the same time being
extremely safe to the patient as long as the proper eye precautions are taken. The
last two illustrations are videos comparing the new class IV cold laser with a
typical Class IV laser. The differences between the two are remarkable.
The last two items really drive home the point of what
makes this Class IV cold laser a truly unique laser. They are pictures and
videos on two types of Class IV lasers. One is a typical Class IV laser which
most medical professionals are familiar with. The other is the new Class IV
cold laser. I did an experiment with two Class IV lasers. The first
illustration is the typical Class IV laser. Now the wattage used with this
laser is in the 6-watt range. This would probably cause a burn to the skin at
this power especially if it were kept in the same spot. On the other hand, the
second image is the true Class IV cold laser. Notice the difference in light
I suspect this new Class IV cold laser may be a game
changer. The preliminary results in the office are quite impressive. We are
truly making use of photonic energy to make a difference. Time will tell, but
this seems to be exactly what we asked for.
Below is the Class IV hot laser shined into a container having a mixture and saline. We can see the red color from the laser is not vibrant. Realize that when the laser is being used on the body it will need to penetrate a mixture of saline and blood.
The next picture and video are of the new Class IV cold laser. Notice how vibrant the color is. The same will happen in your body. Realize that the only difference between these pictures is the lasers. The container is the same container.
This is an especially fascinating study as far as
aging is concerned. I left the article link at the end of my write up. What
this study looked at was the ability of long-lived people to repair DNA damage.
In this particular case they looked at inherited
and naturally occurring genetic changes in older people. They found in the
long-lived population two particular genes COA1 and STK17A. These are rather
esoteric names but the importance is there! COA1 is involved with energy
production and communication between the mitochondria and the cell nucleus.
COA1 performed three functions that are part of the blue prints for anti-aging
platforms. They directed cell response to DNA damage, they prompted badly
damaged cells to die off, and controlled the amounts of Reactive Oxygen
Species. I suspect these genes are stimulating the P-53 gene. P -53 is called
the tumor suppressor gene. Taking things one step further, remember that NAD+ is a substrate for DNA
repair proteins such as PARP1, PARP2 and PARP3 as well as
enzymes that can influence DNA
repair capacity such as SIRT1 and SIRT6. The PARP enzymes
typically get shut off when the body does not have enough NAD+ to go
around. Looks like there may be some
overlap here. Activate the DNA repair genes and you may live longer. At least
you are giving yourself better odds. This is why I feel it is of paramount
importance to take NAD supplements both orally and intravenously. Also remember,
there is much science out there that shows Ozone therapy can increase the NAD
levels in the body in addition to dramatically decreasing damage from Reactive
Oxygen Species. The moral of the story here is:
MAKE SURE YOU TAKE YOUR NAD TO
STAY YOUNG.Here is the article I am talking about:https://bigthink.com/surprising-science/semi-supercentenarians-dna-repairThanks,Dr. P
(The above diagram encompasses most of the external factors that affect stem cells in our body.)
A stem-cell niche is an area of a tissue that provides a specific microenvironment, in which stem cells are present in an undifferentiated and self-renewable state. Cells of the stem-cell niche interact with the stem cells to maintain them or promote their differentiation. We can see that the niche, as we call it, is very complicated and multi-faceted. If we understand the environment of the stem cell we can learn how to make procedures work more efficiently. This is easier said than done. We must realize that when we study the niche it is done in the lab (in vitro) and the results in the lab may not match what happens in real life (in vivo).
Let’s break down the Niche components one at a time. The first aspect we will discuss is hypoxia and metabolism. Hypoxia, or a diminished amount of oxygen, is one of the most significant environmental factors affecting cells in many different ways.
Hypoxia plays an important role in different aspects of cell chemistry such as metabolism, migration, proliferation, differentiation and, apoptosis (cell death). Hypoxia works thru many different elements such as hypoxia-inducible factors (HIFs). These are various growth factors that are produced by hypoxic conditions. HIFs are master transcription factors. This means that they mediate various events in cells. In molecular biology, a transcription factor is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA. More than 1000 genes are targets of HIF, regulated directly or indirectly by it. For example, transcription factors, enzymes, receptors, and membrane proteins can be induced or suppressed by hypoxia. Mesenchymal (MSCs) and Hematopoietic (HSCs)stem cells are important components of the bone marrow niche.
The bone marrow niche is a state of physiological hypoxia. In another word, it is low in oxygen. Typically, when we harvest bone marrow aspirate we like to keep in hypoxic conditions. This may increase the survivability of the cells when they are reinjected into the body. This may be achieved by putting the aspirate in a vacuum container.
In regards to metabolism, some substances are broken down to yield energy for vital processes while other substances, necessary for life, are synthesized. In contrast to differentiated cells (which use oxygen in a respiration system like we are familiar with), many stem cells appear to rely to a greater extent on glycolysis than on oxidative phosphorylation to generate adenosine-5ʹ-triphosphate (ATP). Glycolysis is an oxygen-independent metabolic pathway. Unlike oxidative phosphorylation (the common form of respiration achieved by breathing air), glycolysis can proceed anaerobically (without oxygen). This raises the possibility that the dependency of a stem cell on glycolysis is an adaptation to the low oxygen levels that are present in the body during development and in an adult stem cell microenvironment or ‘niche’. What this really means is that the stem cells are able to survive on very low concentrations of oxygen mainly because they do not have to use oxygen. Realize that when we utilize oxygen for metabolism we will create a byproduct called a reactive oxygen species (ROS).
A ROS is more commonly known as a free radical. ROSs can cause damage to the cells in a variety of ways. They cause damage on a variety of levels. The shift toward glycolysis might minimize the production of reactive oxidative species (ROS), which could indirectly affect stem cell function. As an interesting aside, another aspect of anaerobic glycolysis is that it is energy system of choice for high- intensity activities that last from 30 seconds to about three minutes.
This occurs in athletes. This system has 11 chemical reactions that incompletely metabolize glucose to provide ATP and a byproduct of metabolism that causes acute muscle soreness, namely lactic acid. We can also see that what affects the “stemness” of a cell is the type of respiration it utilizes.
The diagram below is very similar to the first diagram that I demonstrated. It is a bit different. We see that there are a variety of components to the niche. These components act as a symphony orchestra. They are all important cogs in the function of the niche.
The cellular components are very important to stem cell function. These components can have a direct effect on the cell. They will produce certain biochemical compounds which are called cytokines. These cytokines are a method in which cells communicate with each other. There are a few different ways that the cells communicate with each other. I have included a slide from one of my talks that discusses cellular communication. In this case, the effect can be any of the “crines” of cellular communication.
These “crines” are found in a number of different compounds such as hormones, different types of growth factors, and exosomes. They will have either a direct or indirect effect on the cells. Many of these effects are mediated by the secreted factors. Some of these secreted factors can affect the production of messenger RNA. The messenger RNA can turn on certain genes in the cell that was otherwise “turned off”. By turning on certain genes we are able to have cells possibly start doing repair work. I cannot stress the importance of these secreted factors. They can lead to success or failure. The problem we sometimes run into is that the amounts and the actual secreted factors may be less than needed as we age. This may explain why as we age it takes us longer to get over injuries and illnesses.
Another important component in the niche is the inflammation and scarring component. This portion of the niche (first diagram) also involves certain cells. These are very specialized cells called macrophages and T cells. They are intimately involved in our immune system. Our immune system and stem cells go hand in hand. Macrophages can be broken down into two different types. There is the M-1 and M-2 macrophage. The M-1 macrophage will lead to inflammation while the M-2 can lead to a reduction of inflammation. The diagram below further explains this:
This diagram has many different things going on at once. In the middle of the diagram, we see a stem cell. Depending on the cells, environment, and other growth factors in the niche we can see a variety different effects. Some of these effects will be the formation of various autoimmune diseases courtesy of the T cells (think Rheumatoid Arthritis). While the macrophages under the right circumstances can help the release of T-Reg cells which will help eliminate or prevent autoimmune diseases. These effects are not just esoteric findings but have practical implications for real-world medicine. Remember, the cells in our body ultimately achieve the goal of repair. Where and which cells are present and active can cause or prevent serious problems.
The next component of the niche deals with the extracellular matrix. Most cells release materials into the extracellular space, creating a complex meshwork of proteins and carbohydrates called the extracellular matrix (ECM). A major component of the extracellular matrix is the protein collagen. Collagen proteins are modified with carbohydrates, and once they're released from the cell, they assemble into long fibers called collagen fibrils. In the extracellular matrix, collagen fibers are interwoven with a class of carbohydrate-bearing proteoglycans, which may be attached to a long polysaccharide backbone. The extracellular matrix is directly connected to the cells it surrounds. Some of the key connectors are proteins called integrins, which are embedded in the plasma membrane. Integrins anchor the cell to the extracellular matrix.
In addition, they help it sense its environment. They can act as the eyes and ears of the cell. They can detect both chemical and mechanical cues from the extracellular matrix and trigger signaling pathways in response. The integrin concept is very scientific but the concept is very important.
The last niche component to address concerns the physical factors and their effects on the niche. In addition to the influence that an artificial ECM may have on cell shape, there is significant evidence that other physical properties of the ECM may also contribute to stem cell fate or lineage commitment. Cells that attach to a substrate have been shown to exert contractile forces, resulting in tensile stresses in the cytoskeleton. Interestingly, the relationship between these forces and the mechanical stiffness, or elasticity, of the ECM can have a major influence on cell behaviors such as migration, apoptosis (cell death), and proliferation.
This represents a bit of a tour of the stem cell niche.
Although, I have presented this in simplistic terms the niche is a very complicated environment which is getting more and more scrutiny. Is this the most important aspect of stem cell science? Probably not but it is difficult to say what is the most important aspect. Thanks, Dr. P