INTERVIEW WITH DR. HUBERT KIM: CARTILAGE REPAIR AND REGENERATION
[ Dr. Hubert Kim, director of the Center for Cartilage Repair and Regeneration, University of California at San Francisco Medical Center ]
Andrew Schorr:
Treating cartilage injuries is one of the most difficult challenges for orthopedic surgeons. We’ll hear from Dr. Hubert Kim from UCSF Medical Center in just a minute to learn about exciting research to really turn things around. It’s all coming up next on Patient Power.
Hello and welcome to Patient Power sponsored by UCSF Medical Center. I’m Andrew Schorr. If you are injured, you have great gratitude for the trauma team and the trauma surgeon and other specialists who may come into play in putting you back together.
You think of bones and tendons and joints being put back together. One natty problem for orthopedic surgeons has been cartilage, having that be as good as new. Now, we’re not quite there yet, but we’re getting much closer, and Dr. Hubert Kim has been helping lead the way with a wonderful team at UCSF Medical Center. Dr. Kim is director of the UCSF Cartilage Repair and Regeneration Center, and it’s part of a whole effort by the Department of Orthopedic Surgery to make a difference in a key area of orthopedics.
Challenges in Repairing Damaged Cartilage
Andrew Schorr:
Dr. Kim, thank you so much for being with us. Tell us why regrowing cartilage, or even preventing the death of cartilage cells when somebody has had an injury, has been such a long-term problem that we haven’t been able to solve in the past.
Dr. Hubert Kim:
Well, I think cartilage is a very interesting tissue, but what makes it interesting sometimes works against the body’s efforts to repair injuries. Cartilage basically does not heal, and there are other tissues you mentioned like bone and tendons, and they do have a good healing potential but not cartilage. It becomes really critical to in the first place maybe limit the amount of cartilage loss that occurs after an injury, and then to overcome some of the challenges that face us when we’re dealing with the cartilage repair strategies.
Andrew Schorr:
Let’s talk about a specific situation that someone might face. First of all when I think of cartilage maybe because it’s summertime as we do this, and I’m a big baseball fan, I think of cartilage around baseball players or football players. Often you hear that some cartilage problem either ends their season or ends their career. Is there some work you’re doing that maybe could make a difference?
Dr. Hubert Kim:
When you listen to the news or watch the news, they talk about cartilage damage. There are really two kinds of cartilage they’re talking about. The first is the meniscal cartilage. Those are kind of O-rings in the knee that help distribute the load and that’s not what we’re really talking about today. What we’re really talking about is the gliding surface cartilage or the articular cartilage, and that’s a very unique tissue that is able to really withstand tremendous loads and usually lasts a lifetime, but in sports injuries and other types of injuries you can actually knock pieces of this cartilage off or damage it in a way that it no longer functions.
That’s when patients undergo different treatments to try to regenerate or replace the damaged tissue, which is not very good at it yet, and so that’s kind of what we’re looking at. We’re looking at ways to treat cartilage damage after it occurs, and also prevent cartilage tissue loss after an acute injury so that our job is easier, more easier, than it otherwise would be.
Andrew Schorr:
Dr. Kim ,when we think of that smooth gliding cartilage we wish the body could just put it back together, but I understand sometimes the body fills in with kind of a fibrous kind of cartilage that just isn’t smooth. Is that right?
Dr. Hubert Kim:
Yes. That’s correct. So what happens is if the bone under the cartilage is damaged the injury site fills with a mixture of cells that can form kind of what we think of as a cartilage scar, but it just doesn’t reproduce the normal cartilage tissue, and the material that ends up filling this space is kind of a fibrous tissue that doesn’t work as well as normal cartilage and doesn’t last the way that normal articular cartilage does. So that’s one of the really ineffective healing responses that the body has, and so that’s why we’re looking for better ways to regenerate the damaged tissue.
Benefits of Limiting Cartilage Loss After Injury
Andrew Schorr:
All right. Now one part of it is regeneration, and the other part of it is preventing cartilage loss. Help us understand that. So somebody, let’s say, was in an accident and is brought to the emergency room. Are cartilage cells dying? And just like if somebody had a stroke or if somebody had a heart attack and the muscle cells are dying, is that’s what’s going on, and is that what you are trying to prevent further loss of?
Dr. Hubert Kim:
That’s exactly right. When the cartilage absorbs a certain amount of energy, the cells that make up cartilage die, and they die by different mechanisms some of which are inevitable, but there are some cells that are dying by a process that we might be able to manipulate. There’s a process termed programmed cell death that’s kicked into overdrive after cartilage injury. So when we did research looking at pieces of cartilage from patients who are undergoing surgery to address these knee fractures we found that a lot of these cells are undergoing programmed cell death, and so the next line of research that we entered into was to study ways we might be able to block this process and thereby preserve some of the cartilage cells that otherwise would die.
There is strong proof of concept that supports the idea of minimizing the zone of injury or the area of injury the same way that doctors do in the emergency room when people are having strokes or heart attacks. If we can minimize the amount of cell death, we hope that we can preserve as much cartilage as possible. There is some cartilage death we can’t do anything about initially, but there does look like there is a substantial amount of cartilage death that we could potentially at least prevent with relatively simple treatments.
Andrew Schorr:
So the goal is to be as good as new or as close as you can to that, and have joints with smooth gliding full range of motion. So how are you approaching that? We’ve talked about cells. What are you doing in your effort to try to get there?
Dr. Hubert Kim:
On the prevention side, we’re testing different drugs and the conditions that would limit the amount of injury that occurs after cartilage damage. On the joint cartilage regeneration side, our team is very interested in trying to harness the potential of stem cells, adult stem cells, to regenerate the tissue that’s as close to normal articular cartilage as possible.
Research Goals and Clinical Trials
Andrew Schorr:
Adult stem cells . . . I know this is different from some of the other research going on in California and elsewhere. Tell us what that means. Would somebody get some sort of injection of cells, and that could help their cartilage start regrowing, or how would it work?
Dr. Hubert Kim:
This is quite a bit more involved and more sophisticated than an injection. That’s probably not the way that we would want to proceed with stem cell therapy. We’re talking about actually developing a combination of scaffolds that will give guidance to these cells, and also specific instructions to these cells to generate tissue that more approximates normal articular cartilage. Our approach will actually be requiring surgery to implant a scaffold and mesenchymal stem cells and additional cells and signals that will actually get these cells to develop into normal cartilage cells that will produce normal cartilage tissue.
Andrew Schorr:
When you talk about a scaffold, there is kind of lines of cells, cells lined up in a little patch or something like that, and that’s implanted. The idea is that it will fill in with other cells your body will be instructed to produce?
Dr. Hubert Kim:
We will be implanting cells right from the start that will start generating cartilage tissue, and there will probably be some additional contribution from your own repair cells, but the driving force behind the cartilage repair will actually be the cells that will implant into the defect, to the area of the cartilage damage.
Andrew Schorr:
All right, that is so cool. Now it sounds a little out there. Where are we now? Are we on the cusp of making this a reality at UCSF? Where are we with it?
Dr. Hubert Kim:
Well you indirectly mentioned the California Stem Cell Initiative, which is a proposition passed by the voters of California to fund stem cell research, and the mandate for the particular project we’re most interested in is actually to bring stem cell technology to clinical trials within four years, which is as you know a very rapid pace. That has really pushed us to try to find something that’s feasible that we could actually bring to clinical trials in that short time span.
In the grand scheme of things, four years, to us at least, doesn’t sound that far away when we think of all the things that we need to accomplish in that time frame. I’m sure patients would like to see it in four months, but I think it is realistic that we could have a stem-cell-based cartilage repair strategy at least in the testing phases in four years. At least that’s our goal.
Andrew Schorr:
How can patients with these sorts of problems help now or in the near future? How can they help you accelerate your research?
Dr. Hubert Kim:
I think the interesting thing is that most stem-cell-based technologies address a patient population that has a strong advocacy group. It’s interesting even though cartilage injury and cartilage damage and degeneration affects such a huge number of patients and has such a tremendous economic impact. We don’t have the types of advocacy groups that other areas in medicine do. A lot of what governments and institutions devote their energies to are areas where there appears to be a great patient interest, so that would probably be one of the areas that would help people doing cartilage research is stronger advocacy from the patient’s side.
On the other side of the equation is that patients who participate in well-designed clinical trials are not only getting treatment but also they’re really advancing the state of knowledge in cartilage repair technologies. One of the tough things that people in our field are facing is proving that one treatment or one approach is actually superior than another, and the only way to get to those types of answers is for patients to enroll in clinical trials that are done very systematically and done very well. That’s another way patients can really contribute to the advancement of treatments for cartilage damage.
Andrew Schorr:
What is the status of available trials now at UCSF that people could consider?
Dr. Hubert Kim:
We’re about to embark on a phase III clinical trial of an existing cartilage repair technique that in some ways is similar to what we planned on doing, but instead of using stem cells they are using the patient’s own grown cartilage cells. It’s kind of a second generation cartilage repair technology, and in our laboratories we’re trying to develop the fourth and fifth generation cartilage repair technologies. But this particular approach is very interesting and is based on very sound research and has done well to date, and the phase III trials should be starting very soon. Anybody interested in this particular approach to cartilage repair, we’d welcome their inquiries into the state of the trial.
Andrew Schorr:
So the bottom line for somebody, if let’s say a trial could benefit them or the results of your research, would be somebody with injury in particular and maybe down the road osteoarthritis could hope to have smoother, hopefully pain free if we can get there, movement and range of motion. Is that right?
Dr. Hubert Kim:
That’s correct. I think ultimately it’s how patients feel and what they are able to do, and so we need to be able to address cartilage defects, and as you mentioned ultimately entire joints, and that consists not only of the articular cartilage but the ligaments and menisci and all the other critical components in normal joint function.
At this point, I think it’s more realistic to focus on cartilage defects that are a manageable size. We’re not really at the point where we can treat degenerative arthritis that affects the entire joint. We’re at the stage of trying to manage much smaller defects, just parts of a joint or parts of one joint surface that are more like divots out of the smooth cartilage that we’re trying to fill in. Eventually this type of approach may be translatable to total joint resurfacing, but I think that’s kind of the next step.
Andrew Schorr:
So Dr. Kim, are you excited about this because this has been such a long standing problem in your field of orthopedics?
Dr. Hubert Kim:
Yes. I’m very excited. I think it’s time for optimism, and I think that there are a lot of new technologies coming online and that stem cells certainly open up an approach that we just simply didn’t have. I think before we were somewhat limited by the types of cells we could use for cartilage repair, and the ability to manipulate these adult stem cells is very exciting. When combined with other technologies that are being developed it looks like we’re much closer to a good long-lasting solution than we were at any time previously.
It is a time of great excitement in our field. I think that within a decade I feel that we will have some really good solutions to this problem and maybe pushing the envelope towards treating entire joint surfaces, but only time will tell. I mean I think that it’s important that we be systematic and cautious as we go forward, but there is a great deal of excitement and optimism right now.
Andrew Schorr:
Well I know you’re opening a new building there and you’ve put together just a great team and your whole orthopedic surgery department is focused on this, and I know it make a big difference. Dr. Hubert Kim I wish you well as director of the UCSF Cartilage Repair and Regeneration Center. Thanks for being with us today on Patient Power.
Dr. Hubert Kim:
You’re welcome.
