This article is Part 1 of a two-part interview with Dr. Christopher Centeno. Dr. Centeno is an international expert in regenerative medicine and the clinical use of mesenchymal stem cells in orthopedic applications. He is one of the few physicians in the world with extensive experience in the culture expansion of and clinical use of adult stem cells to treat orthopedic injuries.
His clinic in Denver, Colorado, incorporates a variety of regenerative approaches, drawing patients from all over the U.S. who are seeking innovative, non-surgical treatments.
Importantly, he is also visionary behind the revolutionary Regenexx® technology, a procedure which involves extracting a small bone marrow sample through a needle and a blood draw from a vein in your arm. These samples are then processed in a laboratory and the cells it contains injected into the area needing repair, with the goal of delivering large numbers of stem cells to the injured area.
In addition to being the President/CEO of BioInformant, the first and only market research firm specializing in the stem cell industry, I am also patient of the Regenexx procedure. I attempted two surgeries on different continents to treat an orthopedic injury that I sustained while competing as an international rugby player. While neither of these operations were able to address the underlying damage, the Regenexx® treatment gave me a less invasive option and full rehabilitation.
On a professional level, I watched first-hand as the Regenexx technology has bought stem cell therapy into the mainstream. Therefore, it was a significant honor to get to do this question and answer interview with Dr. Centeno. Enjoy!
Interview with Dr. Chris Centeno, Use of MSCs for Orthopedic Applications
Cade Hildreth: How did you get started with regenerative medicine and the Regenexx® procedure in particular?
Dr. Chris Centeno: In 2004, I saw a paper that said, in a rabbit model at least, you could regenerate a lumbar disc. The researchers had done a stab model where they created a degenerative disc, then they injected stem cells in the disc, and they eventually observed the disc regenerate and look mostly normal on MRI. I was very interested by that, so I contacted a local scientist at Colorado State University (CSU). They have an orthopedic research center there. Next thing you know, we got into talking about whether lumbar disc regenerative was possible in humans and we decided to work together.
By early 2005, we went through an IRB and got approval to treat approximately 40 patients. Some of that was spine and some of it was peripheral joint, not because we were horribly interested in peripheral joints at that time, but because the CSU researchers had done work in race horses with peripheral joints and that was quite successful.
So, they basically said to us, “Why don’t you do also treat peripheral joints? We know that works in a large animal model.” That is how I got started. We did that for 2 years and did not charge anyone. It was a totally free study and we eventually treated a bit less than 50 patients. The therapies we used at that time were a same-day bone marrow concentrate and culture expanded mesenchymal stem cells derived from marrow.
The peripheral joints worked really well, while the spine was much more hit-and-miss. We eventually went back to the drawing board and figured out spine procedures, but that happened later in about 2008 or 2009.
Cade Hildreth: You mentioned that an initial paper caught your attention and that you then did a lot of the research to move those findings into clinical practice. Can you describe that process?
Dr. Chris Centeno: The first paper I ever saw was Sakai’s paper, and that was the one that got me interested. It was a rabbit degenerative disc stab model and they were able to mostly regenerate the disc. Since then, I have read a couple hundred papers on this topic and a few thousand on others. While I have been influenced by many different scientific papers, it was the concept that bone marrow and mesenchymal stem cells have regenerative potential in the musculoskeletal system that was my key takeaway.
Cade Hildreth: How has the body of evidence supporting the use of MSCs within the musculoskeletal system advanced over the past decade?
Dr. Chris Centeno: We initially we ended up publishing a few MRI case studies that we thought were interesting, which showed some changes in meniscus volume and cartilage volume in knees. Then, since that time, we established a registry to track patients and published that registry data.
Every year or so I go through and create an infographic of all of the bone marrow mesenchymal stem cell research in orthopedics. I think I did that in August, and at that point, just adding up the “N” of all the different patients that were represented in these PubMed listed studies, there were 5,500 patients who had their results reported in the literature. At that point in August, 33% of those patients who have had their results published in the peer reviewed medical literature were from our registry.
Cade Hildreth: When you say “from the registry”, is that the Regenexx registry?
Dr. Chris Centeno: Yes, it is. Recently, we’ve been lucky enough to have the support of philanthropist John Malone. His generous gifts have recently allowed us to form a non-profit to allow others to start using that registry infrastructure that we have built over the last 10 years. But, up until recently, it has exclusively been our registry.
Cade Hildreth: That is exciting news that you have that strong financial backing.
Dr. Chris Centeno: Yes. John has been a big philanthropist in the area of stem cells. He just gave Colorado State University 45 million dollars to start a translational stem cell institute, with the concept that they would take all of their animal treatments and use that experience to aide translation into humans.
Cade Hildreth: Yes, so much excellent stem cell research has been done in horses, because race horses are valuable enough to merit regenerative medicine investments.
Dr. Chris Centeno: So, I told you initially that there was no spine research being done in horses, which is why we had to rely on some of the small animal studies. However, more recently, John funded a chair at CSU for spine applications in horses, so we’ve now had that academic veterinarian come down to our clinic to try to learn how we approach human spines and to see if they could adapt any of that technology to treat horses. In horse spines, it is a huge problem because the animal is so much bigger that some of the tools that we use become challenging to translate. You just can’t take a human machine and use it in veterinary medicine. It doesn’t have the power to see through that mass of tissue.
So, now we have gone essentially full circle. We learned from the veterinary community how to do peripheral joints. Now, we are teaching them how to do some spine work, because spine is only now starting to become an area of interest in horses.
Cade Hildreth: That is novel that the research flows in both directions. Next question, how does the Regenexx procedure work?
Dr. Chris Centeno: We have a couple of variations of the Regenexx procedure. The one we started with was the cultured mesenchymal stem cell (MSC) procedure, where the cells are expanded in number before being re-injected into the area of injury. We also have a same-day procedure. Because of the regulatory environment in the U.S., the culture expanded stem cell procedure is only performed by a third party through a license in Grand Cayman. The same-day procedure is what we primarily use here in the States. The same-day procedure is a proprietary two fraction isolation, which is a “buffy coat” plus another source of stem cells within the bone marrow.
Both procedures are a three step process. The first step is basically a pro-inflammatory injection for which we received a patent recently. The second step is implanting the stem cells via precise guidance. The third step is a “fertilizer” type step, adding in platelet-based growth factors.
Cade Hildreth: Through what mechanisms does the Regenexx procedure work?
Dr. Chris Centeno: That is a good question. On the same-day procedure, it is probably as much about mesenchymal stem cells, as it is about hematopoietic stem cells, macrophages, and other cells that are in that same-day isolation. For the cultured procedure, it is only the mesenchymal stem cells (MSCs) that are expanded, which as you know are somewhat heterogeneous in nature.
There are a lot of different proposed mechanisms as to how MSCs might exert their effects. These include paracrine, differentiation, exosomes, etc. The vast majority of the stem cell drugs winding their way through FDA approved clinical trials will likely never have an answer to that question.
Cade Hildreth: That is an interesting distinction between the two procedures. There are a range of cellular components that exert their effects in the same-day procedure, but for the cultured Regenexx procedure, it is a mesenchymal stem cell (MSC) specific therapy.
Dr. Chris Centeno: Correct, the cultured version of Regenexx is more of a “pure play.”
What was interesting to us is that in certain applications, like in knee, there is an advantage to a much higher dose of isolated and cultured mesenchymal stem cells, but our registry data shows that the advantage is not huge. However, in hip osteoarthritis, there is a much bigger difference in outcome favoring the culture expanded MSCs.
Meaning, we can say that by reviewing registry data that the patients with moderate to severe osteoarthritis hip arthritis who are treated with the same-day procedure don’t respond as well as those that get the cultured procedure.
This difference in outcome between the knee and hip procedures has lead to a reconceptualization of arthritis. For example, some of the literature right now classifies hip osteoarthritis as a different type of condition than knee osteoarthritis. One of the reasons may be that hips don’t have as many native regenerative cells as knees.
There is also a different phenotype of osteoarthritis that seems to be prevalent in hips, which involves the bone much more aggressively, whereas in knees, bone involvement is rare.
Consequently, it is interesting to see the differences in how patients respond to different procedures. These differences have started to give us clues that maybe two things that we thought were equal, knee osteoarthritis and hip osteoarthritis, really are not the same.
Cade Hildreth: Interesting. How do you recommend one procedure versus the other for patients?
Dr. Chris Centeno: Good question, for hip osteoarthritis that is moderate or severe, we generally recommend that patients go down to the Grand Cayman site to avail themselves of the culture expanded MSCs. Most knee arthritis patients we tend to treat in the states with a same day isolation procedure. In addition, we’ve mined the data in the registry to find aspects of a patient’s condition that will help us decide. For example, hip OA patients that are younger than 55 tend to respond better as do those with more range of motion in the hip.
Cade Hildreth: Do you ever recommend multiple treatments for a patient?
Dr. Chris Centeno: We do sometimes. We ran that registry data couple of years, and what it seemed to show was that there was statistically significant “bump” with the second treatment, an improvement of about 15%. Meaning, if you just look at percentage improvement, if a patient’s first procedure gives them less than 50% relief, then a second treatment will likely add an improvement of about 15%. Again, this type of decision can also be driven by cost.
Cade Hildreth: What types of injury or conditions are most often treated in Regenexx, and are there any conditions that are not appropriate for treatment?
Dr. Chris Centeno: Yes, let’s start with what is not appropriate. Severe, end-stage hip osteoarthritis is a tough condition to treat when there is major bone involvement. Even with the cultured procedure patients are unlikely to have great results. It is probably 50/50 odds or less that the patient will experience substantial improvement.
Having said that, moderate hip osteoarthritis seems to be treatable with the cultured Regenexx procedure. However, any of the more mild conditions, like labral tears, respond well to a same-day procedure.
Another thing that we cannot do well through a needle is treat very large tissue retractions. For instance, in a massive rotator cuff tear, we cannot bring the two ends together through a needle. Or, for a massive ACL tear where there are literally two parts that are separated by an inch or more (3 or 4 centimeters of distance), that’s not going to be appropriate for a needle-based procedure.
As far as the things that are appropriate, I will break them into categories.
As far as osteoarthritis is concerned for the knee, that’s one of the more common things we treat. Our registry data has not shown a correlation between outcome and severity. For instance, the more severe osteoarthritis patients seem to do just as well clinically as those who have more moderate or mild osteoarthritis.
Other conditions that are appropriate for treatment with the Regenexx procedure are ligament or tendon tears, as long as there is reasonable approximation between the tissues. That includes shoulder rotator cuff tears, ACL tears, and similar.
Based on procedural volume, the most common body area we treat is knees. The next most common conditions are shoulder and hip. Next most common are foot, ankle, and hands. We do not treat anything that is not orthopedic related.
Click here to read Part 2 of the interview.
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