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We are one of the few stem cell facilities in the world that is staffed by seasoned board certified orthopedic surgeons. Who can better handle orthopedic problems than a surgeon who is specifically trained to handle these problems from many different approaches? Obviously, what sets us apart from other orthopedic practices is the fact that we also offer the use of stem cells and platelet rich plasma (PRP) therapy as an alternative to or in combination with surgery. We have strived to combine the latest technology to achieve the best result for our patients and are constantly looking for ways to improve our outcomes rather than sitting on our past accomplishments.
Usually when stem cells are discussed, embryonic cells are often at issue. At IRMO we are using another type of stem cell is called hematopoietic stem cells (HSCs). These are stem cells that are found circulating in the blood, fat, and the bone marrow. They produce blood cells (white blood cells, red blood cells etc.). They are very important in the formation of blood vessels. Think of the blood vessels as a supply line and stem cells as an army. An army will cease to exist without a supply line. We utilize the HSCs in helping to produce other types of stem cells which actually help to repair the body. This process is called plasticity. This concept can be seen in the following diagram:
Many facilities outside the United States make use of embryonic stem cells, which outside of the United States are easy to procure. The problem with the embryonic stem cells are the many complications associated with them. Besides the ethical considerations, from a practical point of view, we are still a long way from being able to utilize these cells in a safe and consistent manner. When using embryonic stem cells, you are inheriting any potential diseases that the baby may have. For instance, the baby may have a gene that when past age 50 may cause a tumor. The embryonic cells themselves may act as a tumor since there is no natural check on these cells. Furthermore, these cells are foreign materials to the body, and the body will attack these cells in an immune response. For this reason, the patient may have to be placed on immunosuppressant drugs—much like any organ transplant patient. At least with our present technology, embryonic stem cells are not the answer to the orthopedic problems that we deal with. The FDA has put significant restrictions on the use of this type of cell in humans. Plasticity is the ability of one type of stem cell to turn into a different type of stem cell. We may then go from a stem cell, which produces blood cells, to one which produces cartilage tissue or tendon tissue. When we perform a bone marrow aspiration, we obtain a rich source of these (HSCs) stem cells. The good news is that unlike mesenchymal stem cells the number of hematopoietic stem cells does not diminish greatly with age. We now know that the primary engine of new bone and cartilage formation in-vivo (real life) is through to be the recruitment and differentiation of cells classically defined as hematopoietic in origin. These hematopoietic stem cells are the true workers. In scientific circles these cells are many times called CD 34+ stem cells. This name (CD34+) refers to a marker on the cell surface. The definition of hematopoietic stem cells has undergone considerable revision in the last two decades. The hematopoietic tissue contains cells which have long-term and short-term regeneration capacities. These cells reside in the stem cell niche in the bone marrow. One of the aspects our center strives for is to increase the number of CD34+ stem cells in the circulation. If we increase the numbers of these cells we increase repair potential. We increase the number of these cells by the use of various supplements which have a direct effect on the bone marrow. These cells (HSCs) are the drivers of tissue regeneration not mesenchymal stem cells. They cause the formation of blood vessels (vasculogenesis also called angiogenesis). They up regulate the release of growth factors. They also increase the release of other stem cells from the bone marrow.
We are pleased to announce that we are one of a few centers performing stem cell harvesting and isolation of adipose mesenchymal stem cells. These are the bodies’ supervisors of repair. Mesenchymal Stem Cells (MSCs) are found in the bone marrow, the circulating blood, and in fat cells. These are important stem cells for our orthopedic purposes. They have been used to repair cartilage, tendon, and bone etc.
Your body completely does a cell turn over approximately every six years. Our process utilizes these cells to repair and replace damaged tissue. We do know that as we age the number of mesenchymal stem cells diminish in the bone marrow. This reduction of these cells is actually one of the causes of how our bodies age. Luckily, the supply of fat mesenchymal stem cells stays relatively constant as does the number of hematopoietic stem cells.
Initially MSCs were thought to be the drivers of tissue regeneration. At IRMO, our extensive research and cutting edge technology has made it possible for us to understand the most important job of the MSCs is that they will dramatically reduce ( immuno-modulate) the inflammation in an area affected by an orthopedic disorder. When the inflammation is reduced repair can take place.
The above diagram shows that the mesenchymal stem cells first reduce inflammation (immunomodulation) than they help accomplish repair by a trophic action which involves stimulating other cells to accomplish repair. The trophic effect allows the micro environment around the cell to encourage repair. In summary, people once thought MSCs were drivers of repair, but that is old thinking and needs updating with modern literature results. Are MSCs important? Yes! They are cells supporting hematopoietic stem cells (CD34+), homing, release of signals, and immunomodulation. CD34+ and MSCs- show additive effects when combined. So, having a rich cornucopia of different cells is important for tissue regeneration. Focus on one cell type never does as well as many cell types, even with growth factors added. What other practical evidence is there of Dr. Caplan’s concepts? In Orthopedics and other medical specialties we know patients with horrible looking X-rays are playing golf and tennis with little pain yet patients with minimal changes on X-rays have significant disabling symptoms. This can readily be explained by the fact that certain patients have mesenchymal stem cells that may be eliminating the chronic inflammation observed in osteoarthritis, in rheumatoid arthritis, or with severe focal injuries to skeletal tissues. We also see this from time to time where after stem cell therapy we get little change on x-ray yet the patients become asymptomatic.
There are some centers, which recommend taking the stem cells from the bone marrow and growing them in a laboratory and then injecting them back into a patient. This process may not be the best way to achieve repair of problems. There are studies, which suggest that once the stem cells are manipulated outside the body they lose their effectiveness. Furthermore, there is a suggestion that by reproducing these cells outside the body the genetic makeup of the cells may be altered leading to any number of significant problems. Among other factors, it is believed that the telomeres, or ends of the DNA strands, may be significantly altered. The FDA is currently taking a very hard look at these cells grown in a lab due to these potential problems. We further know that larger numbers of mesenchymal stem cells do not translate into greater success. In 2012, a biologics company called Osiris presented evidence at the American Academy of Orthopedic Surgery that when 50 million cultured stem cells were injected into patients 20% of the patients reported less pain while when 100 million were injected 0% of the patients had less pain.
Any clinic that is involved with stem cells, PRP and regenerative medicine needs to consider the Telomeres or the ends of the DNA strand.
Above, we see a diagram of the Telomere or end of the DNA strand. On the left we see an embryonic (young) cell with a long telomere while on the right we see an adult (old) stem cell with a much shorter telomere. The telomeres are disposable buffers blocking the ends of the chromosomes. They are consumed during cell division meaning every time a cell reproduces it loses a small snippet of DNA. When the DNA reaches a certain critical length the cell is programed to die. This explains the basis of most diseases and aging in general. A good practical example of this phenomenon concerns Dolly the Cloned sheep. Dolly was produced from an adult cell which was induced to reproduce. A new sheep was reproduced or cloned but Dolly died of old age at a young age because her DNA was old. If we can stem the tide on telomere degradation we will dramatically increase stem cell effectiveness. There is an enzyme which eliminates telomere damage and it is called telomerase. The problem is that most cells have the ability to produce telomerase but this ability is turned off or silenced and thus damage continues relentlessly. If we turn telomerase back on or at least slow down the degradation than stem cells will be more effective. We do know certain supplements can help achieve this goal. Our clinic prides itself in recommending these supplements. This may be one of the most important new frontiers in stem cell science and probably all of medicine.
We have solved the problem of small numbers of bone marrow derived mesenchymal stem cells by utilizing mesenchymal fat cells. What was one time thought of as a worthless tissue is a virtual gold mine in regenerative medicine. This gold mine is called Stromal Vascular Fraction or SVF.
SVF is as important as bone marrow for like bone marrow aspirate it contains a cornucopia of regenerative cells. These cells include adipose-derived mesenchymal stem cells, hematopoietic stem cells, adipocytes (fat cells) and attached progenitor cells, T regulatory cells and monocytes, and perivascular cellular components. This may seem a bit technical but it is important to understand about these cells. The adipose derived mesenchymal stem cells exist in such high numbers that it is not necessary to grow these cells in a lab eliminating many of the problems associated with growing cells in the lab. Like other stem cells these adipose stem cells reduce inflammation and cause cells to grow in number and turn into different types of tissues. The hematopoietic stem cells accomplish repair. The fat cells in the fat graft will die and release signals which stimulate other cells to become metabolically active. These metabolically cells stimulate the microenvironment allowing for cellular regeneration. T regulatory cells are a component of the immune system that suppresses immune responses of other cells. This is an important "self-check" built into the immune system to prevent excessive reactions. Many experts in the stem cell field feel fat may be the ideal regenerative tissue since it has everything we need including growth factors, regenerative cells, and the fat itself acts as a 3-d matrix.
These fat cells are obtained in the office with a technique we devised. This is a simple technique performed under local anesthesia. There are only a handful of centers in the United States that are currently using mesenchymal stem cells derived from fat cells. Our clinic has performed 1000’s of these procedures without any problems. We have learned from plastic surgeons that the use of fat cells in surgery many times results in the fat cells being converted to the tissue they are surrounded by.
Also, what sets the institute apart from other facilities is the fact that we at one time were utilizing human growth hormone (HGH). We used HGH because the evidence is overwhelming that it can contribute to cartilage and tendon repair. We no longer use HGH, we are now using Insulin Growth Factor -1 (IGF-1). IGF-1 is the active form of HGH and what is actually responsible for many of the regenerative properties of HGH. IGF-1 is known as a substance, which directly stimulates cartilage formation and tissue repair. The amount of IGF-1 given is small and has little if any other effects on the body. Studies have consistently shown that as we age, our production of HGH and therefore IGF-1 diminishes. The injection of IGF-1 attempts to make up for this deficiency. The IGF-1 injection is typically given with every injection (either PRP or stem cell). In addition to the IGF-1 injections we are using a few other injectable cytokines. We are not able to use any these cytokines on our athletes including high school, college and the professional levels. The leagues would consider this performance enhancement even the dose is only a portion of one day’s dose and actually only works on a molecular level in the micro environment. We do not make the rules we follow them! Certain medical conditions will cause us to defer the use of IGF-1 and the other cytokines. You will need to check with our physicians. We feel that we have made a quantum leap in our regenerative practice by utilizing additional growth factors as part of the overall treatment for our patients. More can be read about this in our section concerning growth factors which are also called cytokines.
Another component of our stem cell treatment consists of Platelet Rich Plasma (PRP) injections. Stem cells injected into an area by themselves will remain relatively quiescent. The stem cells will not function without PRP or some component of it. The PRP contributes growth factors and stimulating proteins, which directly affect stem cells. There are at least a dozen major growth factors. These signaling factors instruct the body to send stem cells to the area of damage and at the same time cause the stem cells to reproduce and begin repair. Less severe conditions can be treated with PRP and HGH injections. Moderately severe conditions may require PRP, HGH and mesenchymal fat stem cells. Finally, the more severe conditions require PRP, HGH, mesenchymal fat stem cells and bone marrow stem cells. Typically, this would represent a significant arthritis of a joint. The bottom line is that with every treatment we perform we are in some way utilizing PRP and HGH (if not contra-indicated) injections.
Another major difference of our facility is the use of certain supplements. These supplements can significantly increase stem cell production in the body. This is done in a safe and efficient manner with over the counter supplements. This is based on research performed at medical schools by world famous stem cell scientists (one of these facilities is the University Of South Florida School Of Medicine). These supplements have essentially no side effects and can actually surpass medications which cost thousands of dollars and have some serious side effects. If anyone thinks supplements are not important this is a foolish notion. We take care of many professional athletes and it is not unusual for them to take between 50 and 100 supplement pills a day. We have noticed that when we harvest stem cells from patients who have been on our supplement regimen their yields are much higher even after a few weeks. More information about supplements can be found in our supplement section.
Another aspect, which we are looking at, is the use of hyperbaric oxygen. We know that hyperbaric oxygen cans dramatically increase stem cell production. A huge misconception is that hyperbaric oxygen causes healing by increasing oxygen to the involved areas. Oxygen is actually toxic to the tissues in high doses. Hyperbaric oxygen will actually work by increasing a compound called Nitric Oxide (NO). What the Nitric Oxide does is stimulate a certain enzyme which dramatically increases the stem cell output from the bone marrow. It is the increased stem cells in the circulation that causes the beneficial effects of the hyperbaric oxygen not the oxygen. The stem cells are causing the repair. These concepts were presented by Dr. Thom at the Univ. of Penn. One of our ideas is to use supplements which increase Nitric Oxide in the body. Interestingly enough we know that Viagra and Cialis will increase nitric oxide and thus probably stem cell output. We think that Nitric Oxide will be an increasingly important topic in stem cell medicine and PRP injections. Further discussion about this topic will be discussed in the near future.The other fields which we feel are very important concern the use of light therapy and electrical current therapy. More can be learned about this in the sections on these entities.
As one can see, the institute has tried to cover all bases. We have combined ideas and entities from different disciplines to create what we call our biological cocktail. We have combined conventional medicine with its foundation in the basic science of HGH, stem cells and platelets with alternative ideas such as supplements. Our treatment plan is a hybrid of a number of different successful approaches, which have caused tissues to heal when typically they did not in the past. We have taken these ideas and refined and improved them to create a far superior protocol than anything out there. Our success speaks for itself. We have performed well over 4000 cases and are still counting. We are approaching results of approximately 85% significant improvement in conditions treated. We do not rest on our laurels but strive to be the cutting edge of the cutting edge.