This is not a trick question. I can actually think of a few places but none fit the category better than a spinal disc does. Disc degeneration is about the cellular microenvironment more so than other areas. Like the moon the microenvironment inside the disc is very hostile on many different levels. The disc environment is essentially a vacuum with no oxygen. The pH of the disc is very acidic which lends itself to causing cell death. The high osmolality and low pH of disk are deleterious factors to viability of stem cells. The next problem that the regenerative cells need to deal with in the disc is the biochemical profile of the disc. By this I mean certain types of chemicals called cytokines and proteinases that attack the cells. The cytokines are signaling molecules which in this case cause inflammation and thus a hostile environment. The proteinases are enzymes that digest and damage proteins of cells which is certainly not a good thing for stem cells. Some feel that a compound called A2M may be of some help in the struggle with proteinases. This assumption may hold some truth but it will not turn the tide. Even if the proteinases could be neutralized, the cells will still be attacked by inflammatory cytokines. A good analogy is to look at these inflammatory cytokines as “potent cosmic rays”. Just like on the surface of the moon, if other portions of the environment don’t get you the cosmic rays (bad cytokines) will. These cytokines are the bad guys. They are called IL-1, IL-6, and TNF. Platelet Rich Plasma (PRP) might temporarily neutralize the cytokines but unfortunately this is just not a lasting effect. They are a good start. We must also remember that injecting a disc might actually cause further degeneration to the disc itself. So, we can see that the environment of a disc is somewhat like the environment of the moon very hostile and unforgiving. What can we possibly do to increase our chances of success?
We would have to start by improving the environment. Right off the bat I can conceive of a few things. We would have to see if we have a disc that may have a tear in its’ surrounding wall. The wall is called the annulus. If it is present than it needs to be sealed. This can be accomplished by using some agents found in the blood and platelets which are able to do this. Once the wall surrounding the disc is sealed than attention needs to be directed to the center of the disc called the nucleus. Dealing with the nucleus is much trickier. We need to deliver “good” cytokines to the cells to nullify the effects of the inflammatory cytokines. Getting the cytokines to the depths of the disc use to be a daunting task. The idea was to inject the disc either with a PRP and/or stem cells. So far, by and large, the results have not been very promising. We need to affect that environment of the nucleus. We have a propriety method of delivering the growth factors down to the disc without violating the disc itself. We have very high hopes for this technology but only time will tell.
So, we have a way that we can eliminate most of the cosmic rays (inflammatory cytokines). Another method might involve the use of lasers. Under the right circumstances, lasers can increase ATP production to increase energy, increases Nitric Oxide production, stimulate mitochondrial respiratory complex. So, we can see there are definitely benefits to the laser when it is used properly.
The big question is what type of cell can we use in the disc to try to regenerate the nucleus? The answer to this is we really do not know. We can look at a few of the candidates. One candidate is a mesenchymal stem cell (MSC). This is a cell found throughout the body. Once of its main purposes is immune modulation. It can change the environment and make it more conducive for cells to accomplish repair. The problem with the disc environment is that the conditions are so harsh that the MSC would have a very short survival time. A hematopoietic stem cell (HSC) can many times help drive tissue regeneration. However, it will run into the same problems as the MSC a very harsh environment. So, the question becomes what else might be out there that can withstand such harsh conditions or better yet even thrive in these conditions. One such group of cells is called a Muse cell. The word MUSE stands for multi-lineage stress enduring cell. I have previously written about muse cells and will update about them soon in another blog. Muse cells come from a variety of sources. One the easiest and best sources of these cells is adipose tissue. In many of the studies these cells were produced by the use of collagenase. Collagenase is an enzyme that is used to break down adipose tissue into its component parts. We do not use this since it appears to be in violation of FDA guidelines on the provision of minimal manipulation. We have found a propriety way of obtaining these cells from adipose tissue in a very simple and efficient way. There are some doctors that state that producing MUSE cells will kill other cells. While that might be true if they are processed in a specific way. What we are doing is to specifically selecting out these cells. These are the cells we wish to use. Those doctors that state that these cells cannot be used are probably correct when they are using their own techniques. This is not the case in the scientific community.
One more thing which may help the survival of the stem cells may be the use of a hydro-gel. One such compound that has had success in animal models is called Laponite. We are also high on one of our techniques. This technique is called “Joint Jelly”. This is made from platelet poor plasma that we process in a specific way. The joint jelly may be a good temporary medium for the cells while they are in the nucleus of the disc.
So, it seems like we may have all the components that may ultimately lead to success in treating disc problems with stem cells. Only time will tell how successful we will be. Thanks Dr. P