We believe the use of growth factors has taken our practice to the next quantum leap. We have been using growth factors to enhance our results with our stem cell and PRP treatments for some time now. Growth factors are signaling molecules that are typically secreted at the site of repair by many different cell types including platelets, stem cells and fibroblasts. These growth factors bind to the cell membrane and start the cascade of DNA synthesis, mitosis and cell repair. Some of these growth factors effect the stem cell environment or as it is sometimes called the “stem cell niche”. It will make the environment much more favorable to the various stem cells.
The technical term for the various growth factors is cytokines. Cytokines—from the Greek cyto- (“cell”) and kinos (“movement”)—are tiny cell-signaling protein molecules secreted by various cells. Constituting a category of signaling molecules utilized widely in intercellular communication, cytokines may be classified as peptides, proteins, or glycoproteins. You might think of the cytokines as the bodies mobile phone system. They can be the difference between success and failure. Cytokine imbalance is responsible for most disease processes.
Cytokines activity is mostly local, but in some cases they impact the entire body. There are several groups of Cytokines or growth factors. These growth factors can act in three main ways. The first is that it can act in an endocrine fashion. This means that the growth factors may affect cells in a distant area. This is similar to our bodies own endocrine system. For instance, our pituitary gland located in our head affects cells in many different parts of the body. The next aspect concerns paracrine action which means that the factors may affect neighboring cells. The last aspect is an autocrine action meaning that the factors affect the surrounding cells. Interestingly enough stem cells work in a very similar fashion. One should think of the cytokines as architects of cell repair. The repair occurs mainly at the cellular level. The area surrounding the cells is called the extracellular matrix.
We must realize that there are both good and bad cytokines. If you have a symptomatic osteoarthritis the chances are that your symptoms are caused by bad cytokines. Two bad cytokines that comes to mind are Interleukin 1 (IL-1) and Interleukin 6 (IL-6). These bad cytokines cause pain, swelling, and typically cell death. When you are causing cell death you are in what we call a catabolic state. This means you are breaking down tissue causing destruction of the cells and eventually failure of the system. Another important bad cytokine is called Tissue Necrosis Factor or TNF. TNF will cause cell death and block repair. In Regenerative Stem Cell Therapy we are trying to counteract these bad cytokines by manipulating good cytokines that come from both stem cell and PRP injections. We are to turn the tide and get the joint or tendon into an anabolic state. An anabolic state means we are now building up tissue.
Three very important good cytokines are Interleukin-1-Antagonist (AIL-1 also called IL-1A), Interleukin 10, and IGF-1. They can override catabolic action of the bad cytokines. What these growth factors actually do is try to modulate or diminish the inflammatory response. We now know this is one of the most important jobs of mesenchymal stem cells. If a significant inflammatory response is present than repair is jeopardized. Realize that the reduction of inflammation is more on a cellular level and thus non-steroidal anti-inflammatories will not achieve this goal.
In addition to modulating the inflammation, the good cytokines actually help repair the tissue. There are many good cytokines that can accomplish repair. I would have to write a book to discuss them all at length. What I would to do is give a brief synopsis of what is probably the more important ones but realize they are all important.
One of these factors is Transforming Growth Factor or TGF. TGF is important in collagen synthesis and tissue repair. This is a major repair growth factor. TGF appears to stimulate macrophages (a form of white blood cell) to secrete various growth factors. It also directs the macrophages and other cells to areas needing repair. Finally, it stimulates angiogenesis (which means that it forms blood vessels). Another important factor is Fibroblast Growth Factor or FGF. FGF helps organize connective tissue. FGF’s functions are similar to TGF but it seems more involved with stimulation of new growth of blood vessels.
Insulin Growth Factor or IGF-1 is the active form of Human Growth Hormone. This is a multi-talented growth factor. It is very important in cell division etc. It is so important that we are giving it as an intra-articular (joint) injection or an injection into a tendon. IGF-1 found in PRP and stem cells. It is secreted by the liver thru stimulation of Growth Hormone. Studies show that IGF-1 stimulates the glucose uptake by cells thus supplying them with more energy. It also inhibits protein catabolism (destruction). It is also believed that it affects cell receptors which drive a stem cell toward the formation of cartilage tissue. It seems to block many of the interleukin inflammatory pathways.
One more important growth factor is called Vascular Endothelial Growth Factor or VEGF. VEGF is important in that it helps to establish a blood supply where typically there is no blood supply. This is a very important concept in stem cell science.
Up until now these specific factors were extremely expensive and sometimes had significant side effects. Previously, it was almost impossible to obtain these growth factors. They are now available and are extremely safe if used properly. The trick is to learn to use them in the proper dosage regimen and combination. Luckily the company we are dealing with is a company that has staff who are the expert’s expert in the field of cytokine medicine. In simplistic terms what we have now achieved is the ability to significantly affect the joints or tendons we are working upon in a very positive way. These factors dramatically increase the efficacy of the stem cells to accomplish repair.
Up until this time we had to depend solely on the body’s own production of growth factors such as those found in a PRP. The problem with the PRP is that the growth factors seem to run out after about one week. Now we are supplementing the cytokine production by giving these factors on an oral basis. We take this two steps further by using cytokines in the form of injectables and transdermal creams. With these different forms of cytokines a more sustained release of growth factors will occur enhancing the repair. We are now utilizing these growth factors on patients on a daily basis. We will prescribe a regimen of multiple growth factors to be taken on a daily basis. These cytokines are what we call recombinant which means they are produced in a lab by bacterial or yeast etc.
Cytokine therapy is one the new exciting fields in medicine which like stem cells has the ability to dramatically change the face of medicine and treatment protocols designed to conquer a variety of conditions. We may come to the conclusion someday that just using these cytokines may eliminate the need for harvesting stem cells. Will these cytokines make stem cells obsolete? I doubt it but only time will tell if this comes to fruition. Cytokine Medicine truly represents a Quantum Leap in Medicine. It certainly represents a Quantum leap in our practice. Cytokines are the building blocks of life. When we master cytokine therapy we will significantly reduce the debilitating effects of most diseases.
To be on the cutting edge of the cutting edge we utilize exosomes with our PRP, Cell-Based and Cytokine treatments. We have a propriety method of obtaining exosomes from the plasma. Exosomes are important in that they help transport growth factors to various areas of the body.