I just returned from lecturing at meeting concerning Regenerative Medicine in Germany. A few of the lecturers mention how mesenchymal stem cells drive tissue regeneration. There still seems to be a misconception out there that mesenchymal stem cells are the cells of tissue regeneration. This is simply not the case. Are mesenchymal stem cells important? The answer is a resounding absolutely! Are they the most important cell? The answer to that question is a resounding no! Why is there such a dichotomy? One fact that has to be mentioned is that there is no one cell that is the most important cell. Nature works like a symphony orchestra. In order to have the best sounding orchestra the musicians need to be in the proper ratio. All components of the orchestra are important. The same hold true for the methods the nature repairs injuries.
Dr. Arnold Caplan has taught us that the new concept for mesenchymal stem cells is that they are medicinal singling cells. What they really do is cause immune modulation. They help manage regeneration. The help prepare the stem cell niche or environment for other stem cells to perform their regenerative duties. Perhaps a good analogy is to think of mesenchymal stem cells as a navy seal strike team. They have a mission to accomplish. They are designed to initially secure an area but the eventual outcome depends upon the other forces coming in and getting the final job done. In the stem cell world many times these other cells will be hematopoietic stem cells which are thought to be the drivers of regeneration. Furthermore, the hematopoietic cells will sought of stage guerrilla warfare. Just like many times in the military the local people will be recruited to join the fight; the local cells will be recruited to engage in the repair. When the local cells get recruited this is called the paracrine effect. This is a very important aspect of stem cell therapy.
The mesenchymal stem cell are many times derived from from cells that are found on blood vessels. The above diagram is from some work by Dr. Bruno Peault. We can see the pericytes which are found on the blood vessels. These pericytes are precursor mesenchymal stem cells. We now know these pericytes provide oversight for local tissue regeneration. The mesenchymal stem cells are many times released from broken and inflamed blood vessels. These cells can analyze their surround and help recruit other stem cells to the area. As more research has been done we now know that there are a number of different type of mesenchymal stem cells. There are a number of different types found in the bone marrow aspirate. The question becomes are we throwing away many of these mesenchymal stem cells when we centrifuge a bone marrow aspiration. They are of different sizes and densities and it stands to reason that some of these cells may be discarded. Perhaps, this may be one of the most important aspects of thee new bone marrow aspiration needle from Marrow Cellutions that eliminates the need for centrifugation. Time will tell.
Thanks Dr. P
Recent research from Harvard University and Hughes Medical Institute has elucidated a new type of cell language. One of the established main methods of intercellular communication is by cytokines. I liken this to the body's cell phone system. Research is giving us a better understanding of the role off various cytokines. Some of these cytokines are the "good guys". They help correct osteoarthritis and other such conditions. While other ones are the "bad guys". They help cause and perpetuate osteoarthritis and other assorted conditions. Perhaps we should think of cytokines as the spoken word. More will be said about cytokines in another blog.
The new language proposed by the Harvard researchers is called NOTCH language. Notch language is almost like sign language. It is more physical than the spoken word. Notch language requires the "speaking" cell to physically pull on the "listening" cell. We now know that a physical force may be crucial to regulating cell division, replication, and a host of other functions. As was said in the article, research has now shown that physical force plays an important role in regulating a variety biological functions. Interestingly, we find mutations in the Notch coding gene in a variety of diseases such as Leukemia. It is now felt that altered mechanical signals in the microenvironment of the cells may lead to many diseases.
Notch signaling makes use of the cell membrane. Cytokines also make use of the cell membrane where a variety of receptors are located. Notch signaling involves a protein on the cell surface which uses mechanical forces to communicate into the cell. The researchers found that in Notch communication there was a point where there is something called a Delta molecule and a Notch molecule. When these two molecules bound together the Notch molecule still is not activated. An enzyme had to be available to allow the Notch molecule to do its work. The mystery was how did this enzyme get exposed. In their research the Harvard group used magnetic beads to tug on the delta molecule and found it activated the enzyme and allowed the Notch molecule to communicate.
This all seems well and good but is there are good clinical ideas that we can take away from this? I cannot say for sure if there is clinical significance to Notch language. But I think there is something very important here. We have performed electrical stimulation on joints to enhance stem cell function and survivability for some time now. There is very good evidence of some of the mechanisms of electrical stimulation. We know that it increases microcirculation in the area. Certainly this is helpful. It also increases stem cell motility to the area allowing the cells to hom to areas of injury. Electrical current also increases growth factors in the area. But perhaps a more fundamental function is what effect D/C micro electrical current has on Notch language. Can the electrical current pull on the Delta molecule to activate the Notch molecule and initiate Notch language. Electrical currents are taking increasing importance in the field of Regenerative Medicine and Cancer therapy. There is some intriguing research in utilizing electrical currents to treat cancer. For have known for years the electrical currents can stimulate articular cartilage formation. This come the work of Dr. Carl Brighton of Univ. of Penn. and Dr. Hugarford of John Hopkins Univ. We have had good success using electrical stimulation. Now I think I have a better understanding of what is going on. Perhaps with electrical stimulation we are helping the cells communicate with each other the spoken word (cytokines) and with sign language (Notch talk). I suspect there is probably some truth to this.
Thanks Dr. P
Even before the days of Ponce de Leon mankind has been intrigued the the quest for true age reversal. We know for sure that starvation will extend life but we are not sure about age reversal. There are many supplements that we know may at least help down aging. Some of these include derivatives of beets, broccoli, and a host of other compounds. It appears that these compounds have a distinct effect on stem cells. These supplements can effect the stem cells in many different ways. They may effect the stem cell environment or as it is also called the stem cell niche. If the environment is hostile than the stem cell has a much less chance of success. Those supplements that effect the niche are many times considered antioxidants. The job of the antioxidants is to neutralize the effect of what is commonly called free radicals. These free radicals occur when the body utilizes either oxygen or nitrogen. We are beginning to realize that Nitric Oxide is extremely important to many body functions. I will talk more about this in another blog.
About a year ago there was some buzz about transfusing blood plasma from young rats to old rats. The results were nothing less than astounding. The researchers found that the old mice had a reversal of many of the aging processes especially in the brain. The researchers found a protein in the blood of the young mice called GDF11. In this case we are not just slowing down the clock but we are actually turing it backward. It is suspected that GDF11 is produced by a very specific stem cell which is starting to attract quite a bit of attention. This stem cell is sometimes called a V cell or very small embryonic like stem cell.
The very small stem cells are thought to be capable of forming almost any type of tissue. For this reason these cells are called pluripotent. As I have eluded to in other blogs these cells may be considered the body’s emergency stem cell supply. They also seem to be implicated in acupuncture. These cells are found in something called Bonghan Channels which are intimately related to acupuncture. The problem with the V cells is that they are normally difficult to activate. However, thinking out of the box researchers have devised ways of turning these cells back on. These are the patients own cells. The methods of turning them back on are proprietary. We have had the good fortune of working with these unique cells with some excellent results. The tantalizing question is if these cells can be harvested from a son or daughter or grandchild and given back to an older related adult. The answer is just around the corner. I can see the hands of the clock going counter clock wise. There will be more to come. Thanks Dr. P
