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Regenerative Medicine

SUPPLEMENTS AND THEIR USE IN STEM CELL AND PRP THERAPY

We now know supplements are extremely important in the field of Stem Cells, Platelet Rich Plasma Injections, and for that matter all of regenerative medicine. We take care of many professional athletes and it is not unusual for them to take fifty different supplements a day. These supplement regimens are designed by nutritional gurus. We have talked to these same gurus to design supplement programs for our patients. Before we talk about supplements we need to go back to the basics. None could better sum up our endeavors concerning supplements and what we are trying to achieve than the following taken from Popular Science Magazine from Aug of 2011. This is an article about my personal friend and colleague Dr. Williams Andrews. Dr. Andrews is the world’s foremost expert on Telomere science. Dr. Andrews and his company Sierra Science (www.sierrasci.com) are testing various compounds which may turn on Telomerase or the enzyme which restores the ends of the DNA strand. I have previously mentioned telomeres in another portion of the web site. The Telomere is the end of a DNA strand that is lost on cell division. As we age the DNA strand gets shorter and shorter until the cell is programed to die. The length of an individual’s telomeres is closely associated with their biological age, and research suggests that control of telomere length has the potential to treat many diseases associated with aging, and possibly to allow humans to live at a physiologically “young” age beyond the current theoretical maximum human lifespan of 125 years. If someone states that Telomeres are an esoteric entity realize that the Noble prize in Medicine was awarded in 2009 for research on Telomeres. What does have to do with stem cells? The answer is plenty since in our procedures we are encouraging stems to replicate in the body. This replication will cause telomere damage and subsequent diminished stem cell effectiveness. This explains why many times younger people can recover from injuries much sooner than older individuals. The younger stem cells with longer telomeres can function significantly better than stem cells with shorter telomeres. Possibly one of the holy grails of stem cell science will involve the stimulation to turn back on the enzyme telomerase which helps to lengthen the telomeres. We only know of two cells which produce telomerase. One type of these cells is our reproductive cells. That is why our children are born young. The other types of cells are certain types of cancer cells. This is why some cancer cells are immortal. In our institute we are striving to at least slow down telomere degradation by the use of certain supplements.

The following diagram ties this all together. This diagram was taken from an article on Dr. Andrews in Popular Science. This slide represents the death spiral of a cell. This slide represents the multifaceted damage that occurs and accumulates. The telomeres shorten causing the activation of a certain gene which starts to repress mitochondrial function. The mitochondria are the powerhouses of the cells. When the mitochondria begin to fail the cell is doomed for failure. It is like a car running out of gas. When the mitochondria fail a host of other bad things happen. Stem cells are no different than any other cells.

DePinho’s attempt at developing a unified theory of late-life aging, “the death spiral,” as he calls it, that can transform a spry, alert 80-year-old into a shell of herself at 90 or 100 even in the absence of diagnosable disease. His mice data suggest that the major aging processes—free-radical damage, mitochondrial dysfunction, and short or damaged telomeres—interrelate and that the telomeres can instigate decline, acting as the first domino that sets in motion the rest. If the telomeres can be preserved, the entire system may be granted at least a temporary reprieve.

The above diagram shows the fields we are attacking and trying to mitigate. We have discussed telomere shortening. Another important aspect in the supplement field of stem cell science concerns the mitochondria which is the powerhouse of the cell. We know that the mitochondria must be at their peak function in order for the stem cells to work properly. One such supplement which helps mitochondria achieve this goal is Melatonin. As we age our bodies become deficient in Melatonin. Cellular biologists have recently discovered that melatonin has an even more basic function, which is to protect oxygen-based life from the toxic effects of…., oxygen. Yes, oxygen. As we metabolize this life sustaining gas, we generate highly reactive molecules called free radicals, which can corrode our cellular membranes and damage our DNA. The process, known as oxidation, weakens our minds and muscles as we age, and contributes to at least 60 degenerative diseases, including cancer, heart disease and Alzheimer’s. The body produces several enzymes to inhibit oxidation, and nutrients such as vitamin C, vitamin E and beta carotene can provide extra protection. But most of these so called antioxidants work only in certain parts of certain cells. Melatonin readily permeates any cell in any part of the body- including the brain. This research has been presented by Dr. Russell Reiter, a professor at the Univ. of Texas Health Science Center. I had the honor of lecturing at the same meeting as Dr. Reiter and spoke to him. Dr. Reiter’s research has recently shown in animal experiments that melatonin can protect tissues from an amazing array of assaults. As far as antioxidants claims go, melatonin has been acknowledged by many researchers as one of the elite antioxidants in the body. Directly and indirectly melatonin is said to exert a powerful antioxidant effect which is metabolized in all body tissue. Some reports say that melatonin is the most powerful anti-oxidant of all. One thing of supreme importance is the fact that melatonin effects all parts of the cell including the mitochondria. We can reverse free radical damage to the mitochondria with melatonin. If we can increase mitochondrial function we will have a very happy and effective stem cell. Perhaps a diagram of free radicals will help people understand better what we mean by free radicals. .

supplements_chart

From the preceding diagram we see what a free radical actually is. It is an unpaired electron in the outer shell of an Oxygen molecule. Antioxidants will neutralize this. The free radicals are cell killers. They damage DNA. They alter biochemical compounds and reactions. They destroy cell membranes. The cells that are damaged by free radicals will go on and cause disease. We must remember free radicals come from 1. The Environment (air pollution, drugs, certain foods) 2. Internal Production from the body 3. Stress Factors (aging, trauma, disease, and infection) 4. Chain Reactions resulting DNA damage. Free radicals can be attacked on many different fronts including a diet, exercise, and other common sense things. Many people always the question what is the best anti-oxidant? There is probably no one correct answer. If I was pushed on the question I would probably say that that glutathione (GSH) is the body’s master antioxidant. It functions both as an antioxidant and an antitoxin and is a major defense system against illness and aging. Our glutathione level actually indicates our state of health and can predict longevity. Glutathione is intimately related to the regulation of the nitric oxide cycle, which is critical for life. Remember the Nitric Oxide is very important in increasing stem cell output from the bone marrow. It is used in metabolic and biochemical reactions such as DNA synthesis and repair, protein synthesis, prostaglandin synthesis, amino acid transport, and enzyme activation. Thus, every system in the body can be affected by the state of the glutathione system, especially the immune system, the nervous system, the gastrointestinal system and the lungs. Raising GSH levels through direct supplementation of glutathione is difficult. Research suggests that glutathione taken orally is not well absorbed across the gastrointestinal tract. It is known that Vitamin D will act as catalyst for glutathione production

Another important factor in our quest to achieve repair of joints and tendons is to use a product which will restore the collagen to these areas. Collagen is a vital component of structural matrix throughout almost all tissues and organs of the body. It is particularly concentrated in skin, bone, tendons and cartilage where it plays a major role in the integrity of joint-related connective tissues. Studies reflect a relationship with collagen not only to normal healthy joint metabolism, but also to collagen-related alterations related to the aging process. Collagen alterations also play a role in osteoarthritis wherein alterations in collagen structure result from an imbalance in synthesis versus catabolism with resultant articular hyaline cartilage breakdown. A special form of collagen (known as Type II collagen) is a crucial component of cartilage, and to the structural integrity of your joints. So boosting collagen is a critical part of rebuilding cartilage, reinstalling those joint shock absorbers, and erasing arthritis pain for good. We are now using a collagen product from Germany which seems to fit all the needs we are looking for. Collagen hydrolysate passes across the mucosal barrier in the small bowel as a complete peptide that is no longer subject to enzymatic cleavage, accumulates in cartilage tissue, and stimulates production of type II collagen (the major protein in articular cartilage) and proteoglycans in the extracellular matrix of cartilage. What this means in common terms is that this is one of the few products that can be taken orally and be absorbed into the blood system and subsequently be delivered to the joint and be effective. In another words it is not broken down by the intestine.

The other quest that we have in our procedures is to stimulate the release of stem cells from the bone marrow. Remember that the cells which we inject into a joint or tendon are much like a Navy Seal strike team. They will secure the area but will depend on other forces eventually getting the job done. In order to accomplish repair the body will have to send large numbers of stem cells (mainly hematopoietic) to the area. One substance which does this is GCSF called granulocyte colony stimulating factor. The problem with GCSF is that it is very expensive and has some inherent risks. We feel that we have found a combination of supplements which can achieve similar results as GCSF without the risks or costs. We have come across a supplement devised at the Univ. of South Florida by Drs. Bickford and Sandberg. These two doctors are two very prominent stem cell scientists who have come up with a formula that dramatically increases stem cell output from the bone marrow. This product is called StemXcell. This product has been shown in the lab to have a similar effect as GCSF only it has built in safety.

Many of the supplements we will use help boost Nitric Oxide (NO) production which is a potent stimulator of stem cell output. Nitric oxide is a powerful neurotransmitter that helps blood vessels relax and also improves circulation. One example of a supplement we use is arginine. In the body, the amino acid arginine changes into nitric oxide (NO). Nitric oxide is a powerful neurotransmitter that helps blood vessels relax and also improves circulation. Nitric oxide (NO) plays a key role in triggering stem cell mobilization from the bone marrow via release of the stem cell active cytokine (growth factor). The suspicion is that arginine can mimic hyperbaric oxygen and by producing NO formation enhance stem cell production. It is also felt that arginine has a direct effect on the pituitary gland and stimulates HGH production. Interestingly enough, there is a good chance the Viagra and Cialis may also release nitric oxide and cause increase in CD 34 stem cells. Presently, the World Anti- Doping Agency (WADA) is looking into this fact especially for the exercising and sports performance. We are also looking into using these compounds to increase stem cell output.

Some of the supplements which we are currently using can be found on the following diagram.

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The supplements we are using are our own propriety combinations and dosages which we prefer not to divulge here. Each of these supplements has a specific purpose in our treatment protocols.

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