Chris Casey:
You're listening to Health Science Radio, a podcast from the historic Fitzsimons Building in the heart of the University of Colorado, Anschutz Medical Campus in Aurora, Colorado. We talk with our researchers who are searching for answers to some of the biggest healthcare challenges. Across the spectrum of healthcare, our scientists explore tomorrow's medicine today. My name is Chris Casey, and I'm the director of digital storytelling here on campus. It's pleasure as always to be joined by my co-host, Dr. Thomas Flaig, vice chancellor for research at CU Anschutz.
Because we are called Health Science Radio, and we like to give a nod to the radio days of yore. Tom, perhaps you could indulge us in a new segment we're calling CU Anschutz's Historical Moment.
Tom Flaig:
It's an official segment. Wow, that's impressive.
Chris Casey:
Yeah, it's an official segment.
Tom Flaig:
I always like to talk about history. There's a lot of history here. We're in the historic Fitzsimons Building, as you mentioned, which opened in December of 1941, so a long time ago. Chris, I like to walk around campus. There's a wonderful new historical marker. For those familiar with the Anschutz Medical Campus, it's just on the west side of the pharmacy building. It memorializes Sharon Lane. Sharon was a nurse here, came to Fitzsimons in 1968, served in several of the medical and surgical wards here, from what I understand.
Then 1969, she volunteered for service in Vietnam. Courageous volunteer work, went to the war zone. Unfortunately, and very sadly, Lieutenant Lane was killed in hostile activities. She was at a field hospital, I think somewhat behind enemy lines. There was a shelling and she died in caring for sick army soldiers at the time. There were several, I think 10 or 11 female soldiers killed in the war, but she's the only female soldier (military nurse) killed in hostile activity in Vietnam. It's a really striking story, and there's a wonderful, very fitting memorial, a plaque to her, her story, on campus just on the west side of the pharmacy building.
Chris Casey:
I've seen that. It’s a very nice memorial.
Tom Flaig:
Very well done. What an apt way to think about the service she provided here on campus and to the larger effort.
Chris Casey:
Oh, thank you. I knew I could get a good nugget of information from you by posing the question.
Tom Flaig:
There's a lot of history here, sir.
Chris Casey:
Well, we will continue that segment in future episodes. I think it's a winning segment.
Tom Flaig:
I'm glad you enjoyed it. I enjoyed doing that. There's a lot of history here.
Chris Casey:
Okay, well, let's move along. We have a great show today. Today we feature a discussion about research that focuses on the development of regenerative medicine approaches for bone and cartilage tissues. We will talk about osteoarthritis, a painful and serious problem that is expected to grow exponentially as our population ages. Our guest today is Dr. Karin Payne, an associate professor of orthopedics at the CU School of Medicine. Karin received her PhD in bioengineering from the University of Pittsburgh where she studied muscle derived stem cells and their application in bone and articular cartilage regeneration. Her postdoc work investigated how the age of the cell donor affects the ability of stem cells to become cartilage producing cells. Her current research focuses on stem cell and biomaterial based approaches to regenerate cartilage injuries affecting the pediatric population as well as adults. Welcome, Karin. It's great to have you with us today.
Karin Payne:
Thank you for having me.
Chris Casey:
Well, I must say, as somebody who's aging, getting up there in years, I won't divulge, I won't disclose my age today.
Tom Flaig:
That'll be a different segment.
Chris Casey:
Yeah, I do have my share of creaky joints and they're getting creakier by the day it seems. I'm personally very excited to learn about these advances in regard to treating or possibly reversing bone and cartilage loss. Karin, could you start us off by just talking about the scope of this problem. With osteoarthritis, how many folks suffer from it, say in the United States?
Karin Payne:
Yes, of course. Osteoarthritis is a degenerative joint disease. Where the tissues in the joint, such as cartilage, break down over time. Cartilage is this tissue that covers the ends of your bones. When two bones come together in your joints, it provides a nice gliding motion. It's a very lubricated tissue, can absorb a lot of water. What happens is that anyone can get osteoarthritis, but it's obviously more common as people age and women are more likely than men to get it. Also, obesity has been shown to play a role in osteoarthritis. There's that degenerative joint disease where the cartilage slowly degrades over time. Also, younger people, if you have some type of trauma where you injure your cartilage or it's been shown if you tear your ACL, your anterior cruciate ligament at a young age, you're much more likely to develop osteoarthritis 15 to 20 years after that injury than if you've never had an injury. All those, that joint biomechanics, can also lead to osteoarthritis.
What happens is over time the cartilage starts degrading and eventually when people say, "I'm bone on bone, I have no more cartilage in my joints," that's really painful. It's estimated right now to affect approximately 32 million Americans.
Tom Flaig:
It's a huge problem.
Karin Payne:
Huge problem. I think with the aging population, those numbers are expected to increase significantly in the next 20 years. In terms of economic burden, the latest statistics are around $136 billion per year.
Tom Flaig:
The current treatment options are fairly limited and somewhat dramatic, right?
Karin Payne:
Correct. I mean, obviously it's associated with a lot of pain. Probably the first thing is exercise has been shown to be helpful if you can strengthen those muscles around the joint. You might be prescribed to do some exercise. Weight management can also help decrease some of that pain. They're obviously are over-the-counter medications to deal with pain. Eventually you could do anti-inflammatory injections into the knee. I mentioned how the cartilage provides kind of this lubrication for the joint to glide. There are also injections that you can get to provide more lubrication in the joint, but eventually as it progresses, the only real treatment is to get a joint replacement, so a surgical approach.
Chris Casey:
Great. Could you talk about how your team is looking into ways to advance the therapies, increase options for therapies for osteoarthritis. Can you talk about your collaboration with Stephanie Bryant at CU Boulder and Michael Zuscik here at Anschutz?
Karin Payne:
Yeah, so my training, as you mentioned, since graduate school, I've always been working in the orthopedic field and cartilage regeneration. My focus has always been on trying to identify progenitor cells or stem cells and how to push them to become cartilage-producing cells. When I came here to Anschutz, I met Stephanie Bryant, who's a chemical and biological engineer at CU Boulder. She develops these hydrogels, or biomaterials, where she incorporates different factors to create a cartilage environment. We started collaborating in terms of putting my cell expertise, incorporating cells into her hydrogels and seeing if we could form cartilage in a dish. Then we moved on to small animal models that have cartilage injuries.
Interestingly, our research, as you mentioned in the introduction, part of my lab works on pediatric cartilage injuries, which are also found at the end of long bones, but kind of sandwiched between the bone. It's called a growth-plate cartilage. We have a whole other area that's more focused on articular cartilage, so that deals more with osteoarthritis and cartilage injuries that would affect more the adult population. Stephanie Bryant and I have been collaborating for probably eight or nine years now.
Michael Zuscik is the vice chair of research in orthopedics here at Anschutz. He came to this campus about five years ago, and he's been an osteoarthritis researcher for the past 20 years. He's done a lot of work understanding the cause of osteoarthritis, how obesity, the gut microbiome can affect osteoarthritis development. He's also done a lot of work on signaling pathways and biological factors that could delay the disease, and lately has also shown that there's certain biological factors that could actually regenerate the cartilage. The three of us got together in the past few years and kind of combined our expertise and the cell aspect, the biomaterials and the biologics, to come up with some neat new ways to try and regenerate cartilage.
Tom Flaig:
That's a great story. You're dealing with a big problem, right? Osteoarthritis is a huge clinical burden for patients. You're trying a really novel approach to that. The exciting thing is to hear about the collaboration, the different expertise that come together to address those big problems. That's the thing. You each have your own area of expertise you brought to the table and you've been working together for maybe three years as a team on this problem.
Karin Payne:
The three of us, yes. Our very first project together was actually the AB Nexus funding that we got. That's what really brought the three of us together.
Tom Flaig:
Love to hear that. That's fantastic. AB Nexus is a special grant program between CU Anschutz and CU Boulder in the university system here, just for this very thing to bring people together to do novel, interesting things across disciplines.
Karin Payne:
Right, so that's really what nucleated the three of us coming together.
Chris Casey:
Yeah. Another exciting initiative that's on the pretty immediate horizon is something called the ARPA-H Initiative, which sounds rather mysterious and is high magnitude, but anyway, I know that's an initiative that's at the federal level. I looked on its website and it has the headline, Biden Harris administration's ARPA-H Initiative launches new program to help joints heal themselves. That's a pretty attention-grabbing headline.
Your team is also part of this initiative, Karin, so could you talk about how it came to pass that you are involved with this initiative, your team, and what your goal will be through this process?
Karin Payne:
Yes. ARPA-H, which stands for Advanced Research Projects Agency for Health, has only been around for about a year. Their goal is to fund kind of these large moonshot type of projects. One of their first programs was the NITRO programs, so really focused on tissue regeneration in osteoarthritis. We heard about it and obviously we're doing research in this field and wanted to learn more. We went to a proposer's day back in June and had three minutes to pitch our idea.
Tom Flaig:
Three minutes.
Karin Payne:
Three minutes, one slide. We kind of heard what everybody else was thinking about. We came away from that meeting thinking, "Well, maybe we do have everything we need to actually apply to this program." Really the challenge with this program, what they're trying to solve, as we mentioned, osteoarthritis does not have, there's nothing that is disease modifying right now. More importantly, there's nothing that can actually regenerate that cartilage. As you're progressing and you're losing that cartilage, there's no way to get it back. The goal is really to come up with ideas and research to try and get that joint back to a normal joint. To reverse osteoarthritis, that's kind of their goal, which is, it's a large goal.
Tom Flaig:
Yeah.
Karin Payne:
We pulled all our expertise. I mentioned Stephanie Bryant, Mike Zuscik, myself, and we also, the other co-PI on the project is Laurie Goodrich, who's an equine orthopedic surgeon at Colorado State that has been working in osteoarthritis for many years. We kind of pulled all our best ideas together to tackle this grand challenge of developing a regenerative medicine for osteoarthritis.
Tom Flaig:
I imagine you've had a lot of NIH grants or these types of grants over the years. ARPA-H is a different mechanism with a different timeline, different approach to it, isn't it?
Karin Payne:
Correct.
Tom Flaig:
Yeah, an exciting way, I think, but a fast-moving way.
Karin Payne:
Fast moving, yeah. I mean, NIH funding is great and it allows us to develop our research and make advances, but ARPA-H is obviously much more fast-paced, slightly different than we're used to. When you think about an NIH grant, you have a small team that can work on it. The amount of money that's being invested in this program is going to allow us to try to develop three separate therapeutics at the same time across three institutions. We're going to have a team of about 40 to 50 people working on this every day, all in parallel and together. I think it provides a lot of fuel.
Tom Flaig:
It's an exciting approach.
Karin Payne:
I really like the team approach. I mean, we're going to be in constant communication. Everybody's going to be working on this on a daily basis.
Tom Flaig:
As I've watched them roll out this program, it's been really exciting. I've had NIH grants over the years, and there's a different focus to those than this, which is a specific problem, specific time, teams across institutions, these quick timelines and results-oriented outcomes. It's really great to see you in the forefront of this new federal program.
Karin Payne:
I think what's also interesting about this program is the emphasis on, I mean, the goal is we want to develop a therapy that's going to be used for osteoarthritis. There's an emphasis on commercialization and trying to understand how much this is going to cost very early on so that it is accessible for all Americans. I really appreciate that about the program: It has to be accessible to all Americans.
Tom Flaig:
Right.
Chris Casey:
Because cost of healthcare delivery is obviously factored heavily into their goals here?
Karin Payne:
Correct.
Chris Casey:
There are different teams working on, as you mentioned, there are teams working in parallel on the same problem as you across the nation. Are there certain stages of osteoarthritis that each team is kind of attacking and they're trying to come up with solutions to regenerate the tissues in a certain stage? Is that something your team is working on?
Karin Payne:
Right. There were three areas that you could apply to. One was an intra-articular and intravenous therapy to regenerate both bone and cartilage for mild, moderate, and possibly close-to-severe osteoarthritis.
Tom Flaig:
Intra-articular would be injection into the joint space?
Karin Payne:
Correct. The IV injection, the idea is that if you have multi-joint osteoarthritis, you're not going to start injecting every single joint locally, so how can you deliver something that goes to multi-joint? They had a third category if somebody wanted to just regenerate a total joint to resurface the joint. You could either apply to all three, to the first two, or just to the third one. We're focusing on the first two – the intra-articular and intravenous therapeutic.
Chris Casey:
I imagine it'll go to clinical trial stages at some point and that kind of thing?
Karin Payne:
Correct. The way this program works, it's a five-year project. The first two years are the discovery phase where we'll be doing kind of basic science research in the lab and maybe some small animal models of cartilage injury and osteoarthritis. The next 18 months has to be in a large animal study, hence our collaboration with Colorado State. The last 18 months is a phase-one clinical trial that we had to propose. That's kind of the timeline.
Tom Flaig:
Those phase-one clinical trials are sort of the first-in-human application of a new therapy. That's again, very exciting.
Karin Payne:
Yeah, so that's all part of our five-year plan.
Tom Flaig:
The phase one is for the intra-articular, the joint injection and the IV?
Karin Payne:
Mm-hmm.
Tom Flaig:
Both?
Karin Payne:
Yeah, it's kind of separate clinical trials for each therapeutic that we're developing.
Tom Flaig:
Each route.
Chris Casey:
Could you talk a little, Karin, about how, we don't want to go too far into the weeds here, but you will be using the biomaterials and how will you leverage the biomaterials and expertise and those as well as creation of organoids? Could you just talk about this precision-medicine application?
Karin Payne:
Sure. I mean, at the basis, this project, the foundation is the biomaterials that are going to be developed in Boulder. Stephanie Bryant is the lead for the project, and then she was able to recruit some engineers that are also working on different therapies that were actually being used for totally different applications, but we kind of are like, "Oh, maybe we can modify them for osteoarthritis." I think that's going to be really neat, bringing in everybody's expertise and trying to really focus on this grand challenge of osteoarthritis. I think the advantage is that we have the biologists here on the Anschutz campus and the clinicians, our orthopedic surgeons are also helping us a lot with some cells that we're isolating. Then we have the engineers that are doing the biomaterials, and we have the biologists and clinicians up at Colorado State. I think that diversity of thought and expertise and everybody coming together and bringing their best ideas forward, is really how we're leveraging that expertise.
Tom Flaig:
I oftentimes say some of the best collaborations in science are where the investigators’ Venn diagrams barely touch. You bring people who know just enough to answer the questions. I think in my own career, and I think what you're talking about now, those are the most exciting, impactful things you can do. Here you've got really a great cacophony of different investigators with different expertise.
Karin Payne:
Yeah, I'm really excited because when we put this together, Stephanie Bryant brought in some faculty. I'm like, "I don't know who these people are, what do they do?" Now that we all kind of got to know each other, I think it's going to be really exciting to try and solve this. I'm not sure if I answered, oh, the cells.
Chris Casey:
Well, there's a designer aspect, right? Design the cells to do a certain function. That's where some of the advances are.
Karin Payne:
Right. I was mentioning the biomaterials, and I think key to these biomaterials, we're going to put biological factors in them that we believe are going to push the cells to become cartilage cells or bone producing cells. My work with Stephanie Bryant with her hydrogels, we create this cartilage environment where cells like to become cartilage in this environment. It's very personalized in the sense of the biological factors we put in to provide those chemical cues, but we also incorporate mechanical cues because cells are very sensitive to their mechanical environment and what they feel, and that can also drive them towards bone or cartilage. Really designing all those cues into the biomaterials to be able to drive the cells to become bone and cartilage.
Tom Flaig:
Can I just ask you one question? I'm just trying to think of this from the patient perspective. Someone's got osteoarthritis, they've had a hip or knee or some joints that's been given progressive difficulty. They tried some oral medications, maybe done some joint injections work for a while, but now they're at that point. If this all works out as planned and I'm very optimistic, what would be the impact for that patient then? When would you use this therapy? Who would you propose using this therapy? What would you hope to be the impact that patients experience?
Karin Payne:
Right. As I mentioned, we're developing several different therapies to really span the spectrum of osteoarthritis. If you're just starting to have some cartilage degeneration, as I mentioned, the program was really, they wanted minimally invasive therapies. They don't want you to open up the joint and go in and do a surgery. It's really focused on these direct injections into the joint, to just deliver a biological factor that's going to get those cells to get activated and start producing cartilage. If your OA is progressing a little bit more and now you have erosions on your cartilage or you have a small cartilage defect that needs to be repaired, in that instance, again, minimally invasive. We've done a lot of research with these biomimetic hydrogels that you could go locally deliver and try to regenerate that cartilage or that bone defect. For somebody that has multi-joint OA and is more progressed, this systemic delivery of different biological factors that will go activate those cells to form cartilage and bone is what we're working on.
Tom Flaig:
You could imagine this patient population being early stage osteoarthritis, where they're starting to develop some symptoms, even maybe more advanced stage where there is a cartilage defect. Maybe it's trying to think about options where you could do that interarticular, that joint injection, which would hopefully help regenerate that cartilage and ameliorate some of those symptoms that they're having.
Karin Payne:
Right. We're trying to really span the OA spectrum with these different therapies. I mean, the benefit to the patient is if you're able to catch it very early and heal that cartilage, then it's not going to progress to osteoarthritis. You're not going to have that pain. It's not going to limit your daily activity and all the pain medicine you may need to take. I think the big problem with osteoarthritis, if you talk to anybody that has it is, it limits their daily activities, right? It's going to affect how you interact with your family, with your children, with your grandchildren, and affects your ability to work. I think anything we can do to kind of regenerate that cartilage and prevent that late stage osteoarthritis will be helpful for patients.
Chris Casey:
I'm just curious, and you've touched on this a little bit, Karin, but maybe you can expound upon it a bit more. In terms of this big team project you're currently working on, how does doing work of this nature, a project with a specific goal, specific timeline, how does that project pose different challenges or offer new possibilities from your standpoint as a researcher?
Karin Payne:
I think the challenge, anybody doing research knows that sometimes things don't work out and you need to repeat them or you need to tweak them, and it could take time. The way this program is designed, it's very fast-paced and you only have two years to do this research discovery phase. We have things in place where if an experiment was not working, we can pivot to something else. I think we've put some things in place and if one therapy's just not working, then we'll have to drop it and just focus on the other one. The challenge is, my lab is isolating all the cells, and if for some reason I don't have enough cells to give to the next person to test, that just slows (the process), everything is intertwined. One person is providing something to somebody else. That can cause challenges. I think we're a great group of collaborators and we're going to help each other out to make this work.
Chris Casey:
Yeah. It helps that you've already established this longstanding rapport with Stephanie in Boulder.
Karin Payne:
Right.
Chris Casey:
How is that to work across universities? I mean, you're working with Boulder, you're working with Colorado State University folks. You're really leveraging a lot of expertise here in the state. I mean, that's kind of exciting.
Karin Payne:
Yeah. It was kind of neat when we went to the proposer's day because the goal of ARPA-H, at least for this program, was that the reason we all got together and had these pitches, is that they were encouraging people to team together. If somebody had an expertise at another institution, you could get together and form these large teams. I think it's really neat that we felt that we had all the expertise we needed within Colorado.
Chris Casey:
Yeah.
Karin Payne:
I mean, we all know each other. The musculoskeletal research community in Colorado, we're a pretty tight-knit group. Even though we're at different institutions, we know each other fairly well. This is the first time we're all working together on one project. That would be really exciting.
Tom Flaig:
It's a great project and it is interesting to think across the three campuses. CU Anschutz is your health science campus in Colorado, CU Boulder doing some of that basic science, that engineering, that bio, and then CSU, Colorado State University, one of the great veterinary schools and great universities in the country as well. It's really fun to see the three institutions working together in this way. I've just been thinking about the potential impact of what you're doing on so many people that are dealing with this disease. It's great to see people coming together, collaborating this way. Again, great work happens from great collaborating teams. You keep focusing on the teamwork together, that's the key thing.
Karin Payne:
Yeah.
Tom Flaig:
That potential impact on patients and going for such a potential big win here. It's really fun to learn more about it.
Karin Payne:
Thank you.
Chris Casey:
Yeah, and as I mentioned at the beginning, my joints in my body thank you and your team's work for what you're doing as well as the millions of people who, as you say, are dealing with this on a daily basis. It will only become a bigger problem. Thank you for the work, Karin, and thanks for sharing the story and the information with us today.
Tom Flaig:
Look forward to your success in the future and learning more about it.
Karin Payne:
All right. Thank you so much for having me.
