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The Flood Gates Have Opened

Having been involved in the Stem Cell field for several years I have seen quite a few changes and luckily these changes are for the better. Sure there are still hucksters out there promising they will cure everything with stem cells. These type of individuals are becoming fewer and fewer. Last week I witnessed a watershed development in the field of Stem Cell regenerative medicine at least as it applies to Orthopedics.

This development was from an article published in the Journal of Bone and Joint Surgery. This is probably the one of the most prestigious journals in the world when it comes to orthopedic conditions. This article was the lead article giving it even more importance. It was entitled ” Adult Human Mesenchymal Stem Cells Delivered via Intra-Articular Injection to the Knee Following Partial Medial Meniscectomy”. This was a double blind study which means that some patients received stem cells and some did not. More importantly, the treating physicians did not know which patient received the stem cells. The patients that were chosen were patients who had a partial menisectomy. In another words they had a portion of their meniscus surgically removed in an arthroscopy operation. I have performed thousands of these operations over my years as an orthopedic surgeon. Most patients did well at least in the beginning but as time moved on I began to see that a certain number of patients began developing osteoarthritis. As was brought out in the article after a partial menisectomy there is at least a ten to twentyfold increase in osteoarthritis. I have noted similar findings with ACL reconstructions. I am now seeing in both my stem cell and orthopedic practice that these patients tend to develop osteoarthritis down the road. Should these patients been given the advice of not having the surgery? I do not think this is the solution. Maybe we are now realizing that arthroscopy alone may not be the answer. In most of these cases surgery was necessary to help eliminate symptoms. The question is what have we achieved in the long run? Quite honestly I am not sure. But I am sure of one thing, eventually stem cells will provide the missing link. If they do not eliminate the need for surgery (and I suspect they will) they will greatly alter the course of post operative results. I have performed stem cell procedures on many patients with torn meniscus injuries for a number of years now with excellent results. However, stem cells will not fix all meniscus tears!

Getting back to the study. It was actually divided into three groups. One group received stem cells, the second group received three times as many stem cells, and the third group only received hyaluronic acid. Hyaluronic acid is very commonly used to treat the symptoms of osteoarthritis. It does not cure arthritis but can on a temporary (anywhere from six months to a few years) basis ameliorate some of the symptoms. The study compared two important aspects. One aspect compared the amount of meniscus regrowth in the three groups and the other comparison dealt with pain.

In the comparison of meniscus regrowth there was some surprises for the uninitiated. In the groups that received mesenchymal stem cells there was definitely regrowth. However the group that received the larger amount of mesenchymal stem cells paradoxically had much less meniscus growth. This is not the first time this has been reported. It seems that higher levels of mesenchymal stem cells seem to cause inhibition of cell growth. This has been documented in other studies. This is a similar finding to what we observe in PRP preparations.

When looking at pain scores the two groups which received mesenchymal stem cells had approximately twice the amount of pain relief as the control group. Another very important aspect of the study was that osteoarthritis increased in at least 21% of the patients who were in the control group but only 6% in the patients treated with mesenchymal stem cells.

There are some very important findings we can take away from this study. First it is considered a Level 1 study. This means that the evidence is very objective. We are not looking at the results thru rose colored glasses. Secondly, It shows the safety of using stem cells. Essentially no adverse reactions were seen from the stem cells.

One concept that the authors brought out was that “there was an ability to protect the impact of the removal of meniscus tissue particularly in patients that already have some signs of osteoarthritic changes”. This is potentially a game changer.

What can we take away from this article? First, I believe this truly significant since stem cells have finally taken center stage. The lead article in JBJS is definitely center stage. The observations that the authors of this article made are very consistent with many of the results we have observed in our own clinical practice. I have seen that stem cells have made a significant change in the symptoms of patients with osteoarthritis. The authors of the article were restricted in their approach in treating the patient. I would like to see a similar study only in this case I would use many of the regimens we have incorporated into our practice. I suspect the results would be much better utilizing mesenchymal and hematopoietic stem cells together. Remember that hematopoietic stem cells are thought to be the drivers of tissue regeneration. What effect would these cells have on the regrowth of the meniscus tissue? The cells that were utilized in the study were cultured adult human mesenchymal stem cells. These were not the patients own cells but were adult cells that were grown in a lab. There is a school of thought that when cells are cultured they lose some of their effectiveness. Also one cell does not seem to do the job alone. There is a symphony of cells that accomplish repair. Perhaps the next study should be a combination of cells say utilizing both bone marrow and fat together. In this case we are getting the major players both mesenchymal and hematopoietic stem cells. Also how about the use of a PRP (Platelet Rich Plasma) to help activate the stem cells that were injected into the knees. Remember the stem cells are the seeds and the PRP acts like the fertilizer. What about the use of oral, injectable, and transdermal cytokines? What effect might they have on the overall results? How about the use of exosomes and supplements? These are questions that stimulate the mind and wet the appetite for those involved in the field of stem cells. I wish to stress that I am in no way shape or form trying to belittle the accomplishments of the authors of the article. Like I stated in the beginning of this blog, this is a watershed article and we should all be indebted to the authors. I hold them in the highest esteem.

Thanks Dr. P


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