One of the most recent exciting and promising areas of science has been the study and use of our own human cellular tissues in the healing and prevention of injury and disease known as BIOLOGICS. Some examples are stem cells (MSC), exosomes, and amniotic fluid.
In the United States embryonic stem cells (ESC’s) are not used for treatment because of ethical and legal issues.
Autograft: The recipient and the donor are the same person. These stem cells are most commonly obtained from adipose(fat) tissue or bone marrow.
Allograft: Cell products are now available in the United States. They are products that are processed and stored in laboratories that are inspected by the FDA. These stem cells can be from umbilical cord and placenta from healthy mothers and their newborn infants in the United States. These mothers and infants are extensively tested to insure no infectious diseases are present in the mother and infant.
These are like tiny packages within the mesenchymal stem cells. They are like a tiny gift within a gift. They are the main signalling or communicator in our bodies. They talk to the other cells to share information and communicate messages of healing, repair, and regeneration to the organs and tissues of the body. This product is used in IV (systemic applications and via Injections. Preventative Medicine @ Bend is please to announce this treatment will be available at our clinic.
This is pure amniotic fluid liquid allograft derived from donated human placental amniotic fluid. This cell product contains hundreds of growth factor, cytokines, proteins,and other naturally occuring nutrients which enable and maximize the potential of endogenous cells that in turn promote cellular repair and regeneration. This product is often used as a non-steroidal joint injection to reduce pain, and inflammation and encourage repair.
In December 2017 I fell on my right shoulder whilst playing ice skating tag with my hockey playing nephews in Canada. I severely injured my shoulder. My upper body workouts were cancelled as I underwent treatment for my right shoulder. 6 months passed, and I felt I was not getting the healing and repair of the tissues expected from my PT, focused exercises etc. During my training in IM (intramuscular) and joint injections and IV biologics in Sedona with Dr. Lanchbury I was offered an opportunity to receive an amniotic fluid injection in my right shoulder. I took the injection. 3 months later i was back in the gym doing full body workouts once again. This personal experience has motivated me to bring these treat ment options to Bend.
CATCHING STEM CELLS (Special thank you to Dr. Forest Lanchbury for helpful contributions for this article)
I initially became interested in stem cell science and clinical application as I attended a seminar for doctors where the results that were presented were amazing. I wanted to learn more and I developed an ardent desire to help my patients with this new treatment modality. What I have discovered is that the discipline of regenerative medicine includes many distinct aspects of application. Stem cells and the products of stem cells are the major way that replacement of old, or injured cells and tissue occurs. Regenerative medicine includes anything that enables the body to renew and repair itself. Stem cells can both renew themselves and create new cells of whatever tissue they belong to and in many cases other tissues. Bone marrow stem cells, for example, are the most primitive cells in the marrow. From them all the diverse types of blood cells are descended. Bone marrow stem cell transfusions (or transplants) were originally given to replace different types of blood cells. Another very important aspect of stem cells is that they secrete individual substances or packages that can influence other stem cells or mature cells that encounter these substances or packages. These packages are called exosomes. The influence that they have on other cells is called a paracrine effect. These exosomes contain messenger RNA and micro RNA and inform the targeted cells to transcribe certain growth factors and other factors that lead to renewal and regeneration.
TYPES OF STEM CELLS
Stem cells are often classified on the basis of what their potential is, or how many different tissues can one stem cell potentially form. Following this classification we call them Totipotent, Pluripotent and Multipotent. Examples of these types of stem cells are the following; I. Totipotent: Egg Plus Sperm forms a zygote which is a stem cell that can develop into a complete organism II. Pluripotent: The early embryo stem cells which can form all the different germ layers in the body, which means they can form any tissue, but not the complete organism. III. Multipotent: These are adult stem cells. They are found mainly in fat and bone marrow in the adult but also other areas like the heart (cardiac stem cells). The major example of adult stem cells are mesenchymal stem cells which originate from the mesenchyme tissue in the embryo. These mesenchymal stem cells or abbreviated MSCs are the main cells we use for stem cell therapies. In the United States embryonic stem cells (ESCs) are not used for treatments because of ethical and legal issues. Embryonic stem cells are very potent and can develop into any tissue in the body. On the one hand their potency makes them very attractive, but on the other hand this makes them quite difficult to control and they can develop into types of tumors like teratomas. Teratomas contain all the germ layers found in the embryo, so they often contain teeth and hair, vascular tissue and nerve tissue. Teratomas are a totally disorganized growth of all the tissue layers. Much of the current research is focusing on getting better control of the ESCs before they can be routinely used in therapies. One way to get around the embryonic stem cell problem is to try and induce a cell to become like a ESC and then use this cell to form specific tissues . These cells are called: Induced pluripotent stem cells, or iPSCs. iPSCs are genetically reprogrammed cells, iPSCs are almost exclusively used in research. This brings us back to the adult stem cell that we are able to use today for stem cell therapies, the adult stem cell, or MSCs.
SOURCES OF ADULT STEM CELLS
Adult stem cells or MSCs a can be obtained from the same individual that is receiving treatment. This stem cell treatment is called an autograft (self to self). The cells can also be obtained from one individual and then transplanted in a different individual, and is called an allograft. Taking stem cells from fat or bone marrow and then transplanting those cells in the same person they were obtained from is therefore an autograft, or the cells would be referred to as autologous stem cells. Taking stem cells from the umbilical cord, or placenta and transplanting the cells in another person would be an allograft. In both the autograft and the allograft the cells are MSCs since they originated from mesenchymal tissue in the embryo.
AUTOGRAFT STEM CELL TREATMENTS
These stem cells are most commonly obtained from fat (adipose) tissue or bone marrow. In the case of adipose derived stem cells, a liposuction procedure must be performed and then the fat processed to isolate the stem cells from the fat. There is a lot of fibrous tissue in fat and vascular tissue and must be removed. The stem cells are mostly attached to the very small blood vessels (capillaries) in the fat. They are called pericytes when attached in this manner. There are two ways to isolate stem cells from fat. One is with an enzyme called cellulase and the other is without the enzyme. The FDA is not fond of the cellulase enzyme usage as they feel it can cause damage to the stem cells during processing and may also damage the tissue when injected if not completely removed. Therefore, efforts are now directed at processing the fat without the use of cellulase enzyme to isolate the stem cells. Bone Marrow is obtained by aspiration, usually at the posterior iliac crest area in the pelvic bone. Bone marrow derived stem cells have been studied the most in stem cell treatment of knee osteoarthritis. There are definite advantages and disadvantages to both. Generally bone marrow has less stem cells per gram of tissue then fat does. As a person gets older there are less stem cells in bone marrow. Stem cells also decrease in fat, but not to the extent they decrease in the bone marrow. Both adipose derived and bone marrow derived stem cells loose there proliferative capacity as a person ages. That is to say, the MSCs slow down and don’t divide as much. There are also less growth factors in the older aspirates. This means the paracrine effect explained above is attenuated with age. Both fat and bone marrow harvesting require invasive procedures. They both carry risks of infection, pain and post operative swelling. In some cases fluid collections occur following fat aspiration that require draining. Scarring can also occur.
ALLOGRAFT STEM CELL TREATMENT
Allograft cells are obtained most commonly from either umbilical cord, placenta amnion membrane or both. Only recently have these cells become available to regenerative medical physicians. This has created an explosion in stem cell treatments through out the USA. The labs that produce the products are required to be inspected by the FDA and must show proof of arduous testing for infectious diseases in the harvested tissue. They can then sell the products to physicians who use the the products for stem cell treatments. (2018) marks the 30th anniversary of the first successful umbilical cord blood (UCB) transplantation performed in France in Oct. 1988 in a child with Fanconi Anemia. So umbilical cord blood has been used for a long time and has proven to be safe when proper precautions are taken. The FDA has approved umbilical cord blood for treatment of of patients with blood cancers such as leukemias and lymphomas, as well as certain disorders of the blood and immune systems, such as sickle cell disease and Wiskott- Aldrich syndrome. That being said , they have not approved UCB for any other treatments. Human stem cells from umbilical cord have extensive engrafting capability that exceeds that of adult bone marrow. in addition the cells can be frozen for more than 20 years with very efficient post thaw survival numbers. Cells from human umbilical cord and placenta do not usually cause a reaction in the body called graft versus host disease (GvHD) and exact match is not necessary for several reasons. Because they have an age of just nine months, Umbilical cord blood (UCB) cells have underdeveloped HLA markers (these are markers that stimulate the immune system), so you don’t need a close match with UCB cells to avoid the immune response. Because UCB mismatches are widely tolerated in patients, it’s possible for patients to use umbilical cord blood derived stem cells and their signaling molecules to enjoy a greatly reduced risk of GvHD or a tissue rejection event.
STEM CELL PRODUCTS
These products include growth factors and cell signaling molecules. This also includes exosomes produced by stem cells which are 40-200 nanometers and contain Messenger Ribonucleic acid (mRNA) that sends messages to other cells to produce growth factors and healing substances. Exosomes can be used to treat injured and diseased tissues. These stem cell products are powerful and can be concentrated by sequential ultracentrifugation and micro filters. Exosomes are derived from multivesicles. They are present in almost all body fluids. Exosomes from mesenchymal stem cells contain messages from those stem cells to communicate messages of regeneration and renewal to body systems and organs in need of repair. This can result in miraculous healings, such as burn victims healing without scarring, like this deep 2nd degree burn. https://kimeralabs.com/
OTHER REGENERATIVE THERAPIES
In addition to stem cells and stem cell products there are other interventions that assist and attract stem cells which leads to regeneration of diseased and injured tissue. One of the first regenerative therapies was platelet rich plasma. Platelet Rich Plasma (PRP) : This can be a very effective treatment all by itself or as an adjunctive treatment to stem cell therapies. PRP acts like a magnet and is a fertilizer for stem cells. Many stem cell procedures work best when a diseased or injured joint is first injected with PRP. The procedure is quite simple to carry out. Blood is drawn from the patient and then spun down using centrifugation separating the blood from the serum. On the top of the red blood cells are white blood cells and floating above them are the platelets. Above the platelets is platelet poor plasma (PPP)
Platelets, are an important reservoir of growth factors in the body and play an important role in many processes such as coagulation, immune response, making new blood vessels, and healing damaged tissues. PRP also contains a few circulating stem cells although it’s not a major source for stem cells in the body. When PRP is injected into the body it activates platelets which release several healing factors. Most of these are types of growth factors such as platelet derived growth factor, vascular endothelial growth factor, transforming growth factor and several others. These growth factors can be used to heal wounds such as chronic skin ulcers and for healing injured tissues and joints. PRP is also used in anesthetics for improving hair growth and treating the aging face.
Platelet Poor Plasma (PPP) also contains growth factors. One very interesting and effective healing component of platelet poor plasma is Alpha 2 macroglobulin (A2M). It is one of the largest plasma proteins and inhibits damaging proteases in the joint
A 2 M can be concentrated from the PPP and injected in joints to help the affected joint heal. There is a test developed now that can tell you if a patient will get relief from an A2M injection. The test is called a FACS test. A positive test on aspirated joint fluid means there is a 90 percent chance the patient will get relief from an A2M injection. A2M can be used like PRP prior to stem cell injections to help clean up a chronically inflamed joint and make the chosen stem cell therapy more effective.
Prolozone : This is a technique that combines concepts from neural therapy, Prolotherapy, and ozone therapy. It involves injecting various combinations of procaine, anti-inflammatory medications/homeopathics, vitamins, minerals, proliferating agents, and a mixture of ozone/oxygen gas into degenerated or injured joints, and into areas of pain. The result of this combination is nothing short of remarkable in that damaged tissues can be regenerated, and otherwise untreatable pain can be relieved and even cured in some cases. An excellent explanation about prolozone therapy can be found here; http://journalofprolotherapy.com/prolozoneregenerating- joints-and-eliminating-pain/
Ozone combined with P R P is very powerful for regeneration. The injured tissue can be energized with ozone and the cells increase oxygen utilization to heal and repair.
THE FUNCTIONAL APPROACH TO REGENERATIVE MEDICINE
Functional Medicine is a systems biology–based approach that focuses on identifying and addressing the root cause of disease. Each symptom or differential diagnosis may be one of many contributing to an individual’s illness. Regenerative procedures will work much better when we take the functional holistic approach to the patient. This means a careful review of the patient’s history and all the contributing factors to their underlying condition that could be helped by stem cells or a regenerative procedure. The illustration above illustrates all the possible root causes of a patient’s illness. Ideally the roots of the illness should be identified and addressed before administering the regenerative treatment. For example, since we know hormone imbalances, nutritional deficiencies and intestinal diseases have a major contribution to inflammation these should be identified through history and diagnostic testing. Then conditions such as intestinal inflammation, hormone deficiencies and vitamin mineral deficiencies can be corrected prior to the procedure. The patient then has a much better chance for a positive outcome and their money was well spent. Simple things like at least a 14 day detoxification program and correction of vitamin D and omega 3 deficiencies can have a huge impact on success. Stem cells have to eat too and don’t do well in toxic environments. They need the proper fats and amino acids and vitamins to perform well. I have treated hundreds of patients. Without a doubt the patients that have done the best, have implemented the nutritional support got serious about detoxification, balanced their hormones and continued with lifestyle changes. I am very concerned about the direction I see medicine going today. Unfortunately it has seems inevitable that regulatory agencies are going to step in and tell us how we will practice medicine. In the future it is very probable that only stem cells approved for specific indications will be allowed. Big Pharma will have the patents, synthetic cells like iPSCs will have control and the price will go up a hundred times or more. I believe there will still be preventative therapies we can use like ozone, nutritional support, metabolic balance and endocrine optimization. If we combine these therapies with a healthy lifestyle they work very well.