I just finished IOF 2020 and it was a fantastic two days. I wanted to highlight some of my favorite take-homes from day 1, as I have to say that I picked up a few pointers that will be immediately be used in the clinic and a few new clinical and lab research projects were birthed. Let’s dig in.
IOF 2020 was held in Denver, but next year it will be held in Scottsdale, Arizona. Here’s who was there:
I founded IOF about 6 years ago because our field needed a few things. First, it needed a true dedicated orthobiologics non-profit that wasn’t tied to any company or individual. It also needed education and standards. Finally, that organization needed to be set up to take on a life of its own, eventually lead by many with diverse backgrounds and experiences.
Regrettably, that wasn’t going to happen without lots of money, so I secured several million dollars of funding from philanthropist John Malone. Next, it needed to be set up, nurtured, and helped until it could walk on its own. So let’s review how that happened.
IOF was begun to focus on training, education, and standards for interventional orthobiologics. To do that it needed a curriculum. While I birthed most of that, I also knew that once the organization got on its feet and began to walk its own path that it would redevelop all of it. However, the focus would still remain on a set of skills and courses to standardize education. Meaning the problem that still exists to this day outside of IOF is that while we have courses, what you get taught varies by your instructor. meaning there is no set curriculum.
While I and my colleagues at Centeno-Schultz taught most of the early courses, the next step towards IOF’s independence was finding new instructors. So I began to formulate my “get hit by a bus” plan. Meaning, let’s set this organization up so that if I got hit by a bus, that it would still exist and flourish. Next, I needed to begin succession planning so that IOF could be lead without my input. That culminated in me corraling Gerry Malanga at IOF 2017 and asking if he would take over. Why Gerry? First, he was highly capable and had a different skill set than I possessed. Second, he wasn’t part of Regenexx. Third, in many ways, he held many different clinical beliefs, but we both had a love for research and outcomes.
Finally, I handpicked a second successor in Rahul Desai who was also very different. Rahul is an interventional radiologist who uses dehydrated amniotic tissue to enhance many of his procedures. He also held different points of view on the use of mid-levels and had different clinical protocols than the ones I depend on every day, but again, there was that love for “it’s all about the outcomes”.
Seeing Your Child Walk On Its Own
IOF 2020 was a blast for me not only because I learned a few things and the content was fantastic, but also because it was the first time I knew that this thing had its own legs beyond just me. It may seem silly that you put thousands of hours into something and then not retain absolute control. However, all great organizations have one or more leaders who set up the basics, but who then let the thing develop and thrive by getting out of the way.
As I looked around this year, it was amazing to see that what Gerry had done over the last year (with the help of Jillian Abrahamson and countless volunteers) was to install a committee infrastructure that was beginning to get things done. While I personally hate committees and would never have done this, it needed to be done. In addition, Gerry had attracted different thought leaders than I would have and they have already begun morphing the educational program that I birthed. In addition, the diversity of ideas being presented at the conference was greater.
So at the end of the day, since for the first time I could be an observer, what I saw was an organization that was walking its own path all by itself. I felt like a father watching his kid walk for the first time or ride a bike or leave for college. I was very proud.
IOF 2020 Highlights
First, Gerry stepped down and Rahul Desai accepted the presidency. In addition, the board voted in Don Buford to replace Rahul as President for next year, so while we have two orthopedic surgeons on our board, next year will mark the first time the organization will be lead by a surgeon. We also changed the name of the organization from Interventional Orthopedics Foundation to the Interventional Orthobiologics Foundation to better fit a diverse and growing membership.
My Day 1 Lecture Takehome Messages
We began the conference with Diego Correa, M.D., Ph.D. from the University of Miami. He discussed his research developing a new mesenchymal stem cell line derived from the infrapatellar fat pad. He had found that MSCs expressing CD10 on their surfaces ended up migrating to the inflamed synovium of an animal model of osteoarthritis. While there, they converted M1 pro-inflammatory macrophages to M2 normal macrophages.
What’s a macrophage and what does it have to do with knee arthritis? Macrophages are those cells that act as the cleanup crew in the construction site that is your knee. Normal M2 macrophages take away the debris caused by the normal breakdown and repair that happens due to wear and tear. However, certain disease states like metabolic syndrome (obesity, high blood pressure, high triglycerides) can activate macrophages into the M1 state where they begin to eat up normal cartilage. So a cell that switches them from the bad “pac man” M1 state to normal M2 state is a good thing.
Next up, we had a talk given by the Godfather of MSCs, Arnie Caplan, Ph.D. who first coined the term in the 80s. We wanted Arnie to talk about exosomes, given that this was a hot topic right now. Basically, Arnie showed us that the idea behind exosomes is very old. The first uses of “conditioned media” or using the stuff that cells grew in to try to heal tissues goes back decades. In addition, the idea of exosomes was hatched in the 60s. So that my readers know, exosomes are tiny little packets excreted by cells that allow cells to talk to each other.
The main problem for turning exosomes into a drug product that can be legally sold is that it’s all very complicated. First, you need to prime the cells to be able to do some function. You then need to capture the fraction of those exosomes that are focused on that repair job. You then have to scale all of that and ensure that the type of exosomes you have are 100% consistent vial by vial. Regrettably, all of that will take decades. Hence, and this is my commentary, the stuff you will be treated with today that is illegally being sold and called an exosome product is not consistent nor may not even contain any exosomes capable of healing you.
Alberto Panero, M.D. then spoke on his testing of several Amniotc products. He worked with UC Irvine to test these products and they found no viable stem cells. Similar data can now be found in several studies including those initially conducted by IOF, CSU with our lab, as well as Lisa Fortier at Cornell that all show that amniotic and umbilical cord products have no living stem cells. Also interesting in his lecture was that when his group compared the growth factor levels from fresh amniotic fluid to these off the shelf products, there was a steep drop off between the two. Meaning the fresh fluid from the OB ward had a far higher growth factor content than these processed products.
Again, this talk is important because we have countless clinics committing consumer fraud daily by claiming that they are performing amniotic or umbilical cord stem cell treatment, when in fact the products that they’re using have no live and functional stem cells.
I then got up and gave a talk on a recent Delphi panel conducted to establish best practices for use of bone marrow concentrate (a same-day bone marrow stem cell procedure). We were able to recruit many academics from universities such a Cornell, Mayo, Emory, Stanford, etc… as well as a dozen private practice physicians and get them all to agree on how physicians should be using BMC. This included orthopedic surgeons, PMR physicians, sports med, radiologists and others. They all agreed on the need to use a registry, the need to publish results, the use of expanded informed consent, waiting for certain levels of evidence before using BMC for new applications and many more best practice recommendations. The results have been submitted for publication.
As a bigger issue, and an undercurrent in the conference was the attacks on physicians by bench scientists. My concern has been that these scientists are looking to get rid of any type of orthobiologics and scored a recent success in Canada. This is a dangerous trend for patients, as their access to innovative care will be thrown out the window with truly exploitative care. Hence, unless physicians act and do more of these sorts of Delphi Panels to establish and then enforce guidelines, orthobiologics will be the proverbial baby thrown out with the bathwater.
Ken Mautner, M.D. from Emory then got up and discussed platelet-rich plasma (PRP). One of the more interesting take-home points is was that we all need to be careful when we see papers published on PRP. He brought up the example of a recent randomized controlled trial that concluded (in opposition to other papers that went the other way) that PRP was ineffective for rotator cuff tears. However, digging deeper, you saw that the paper didn’t actually use PRP (which is usually defined as at least 3-5X concentrated platelets), but some dilute version of it at 1.65X!
Ken’s presentation brings up interesting points. While we have some data that certain preps of PRP may work better for different clinical indications like knee arthritis or tendon tears, much research remains to be done! For example, to review how complex this all is, we know that each platelet has a different growth factor content between individuals. Hence reporting the dose of platelets is good, but only part of the story. Or take for example that our published data shows that younger and older cells respond to higher platelet doses differently. Young cells quickly max out their additional growth when exposed to higher platelet doses while older cells have a direct dose-response relationship. Meaning the more platelets you use with older cells, the more they grow!
Next up was Jeremy Magalon, Ph.D. from France who discussed his extensive efforts to quantify what different PRP systems produced. For example, in looking at platelet dose and red and white blood cell content, each automated system he tested produces a different product. Interestingly, his data seemed to show that red and white cells may be undesirable. Meaning red and white cells may impair platelet function.
I have been saying the same thing for many years, as our in-vitro data with MSCs clearly shows that when we use “red PRP” with lots of red and white cells, the stem cells in culture don’t grow as well as when we use amber PRP with low WBC and RBC counts. Hence our usual “go-to” has always been highly concentrated amber PRP rather than the lower concentrated red PRP.
Then we had Steve Sampson give a talk on the use of intraosseous (IO) PRP to help treat knee and hip osteoarthritis. This technique involves injecting the bone with PRP in patients who have arthritis as well as also injecting the joint. 99% of PRP injections are only done in the joint and the bone is often ignored. Steve presented data from a group in Spain that has been injecting IO using ultrasound. They were able to take knee arthritis patients who were non-responsive to intra-articular (inside the joint) PRP injections and get them to respond nicely by injecting the bone. The group also found that injecting using fluoroscopy was as efficacious as using ultrasound.
We have been injecting IO for many years with both BMC and PRP. We presented some data last year at IOF (which has been submitted for publication) that showed that injecting the bone didn’t help knee arthritis patients more than just intraarticular. On the other hand, Phillipe Hernogou has a large case series where all he did was inject the bone and the knee arthritis patients did well. So we now have several papers out there where we will need to sort out if injecting the bone is best or needed.
Finally, we had a lecture given by Don Buford, M.D. an orthopedic surgeon who will be the IOF president next year. Don focused on the use of PRP in knee surgery. Interestingly, a large trial showed that it helped meniscal repairs, but not ACL reconstructions. Don’s thoughts were that the reason that it didn’t help ACL surgeries may be the fact that by drilling the graft tunnels, the surgeon is already causing so much bleeding that the joint is already getting flooded with platelets.
The idea that orthobiologics may help surgical outcomes in hotly debated by orthopedic surgeons. Some surgeons are drinking that Kool-aid and others have absolutely said “hell no”. The research is still evolving, but I suspect that we’ll find that we can improve the outcome of many surgeries by adding specific concoctions of orthobiologics.
The upshot? It’s great to see IOF grow up and walk on its own. Kind of like seeing your child walk or ride a bike for the first time. My sincerest hope for the organization is that it continues to grow and walk it’s own path, just like I want all of my own children to follow theirs. My mom used to say that we have no copies in our house, meaning all of her kids were expected to do their own thing. Looks like IOF is off to a great start of doing its own thing!