Dr. Arnold Caplan, “Arnie” to his thousands of colleagues and friends around the world, died at age 82 on January 10, 2024.
Dr. Caplan’s was professor of biology and director of the Skeletal Research Center at Case Western Reserve University. He also was the lifetime achievement award winner from the Tissue Engineering and Regenerative Medicine International Society.
Dr. Caplan’s unifying vision of regenerative medicine lived within an exceptionally creative, warm, and generous mind. His legacy will drive musculoskeletal care for generations to come.
Arnold Caplan spent 54 years at Case Western Reserve University. In that time, he mentored and touched the lives of 150+ researchers. He was a fixture at scientific meetings throughout the world and received many awards including The Marshall R. Urist Award; The Tissue Engineering and Regenerative Medicine International Society Lifetime Achievement Award; and the Case Western Reserve University Faculty Innovator Award.
In 1992, he founded Osiris Therapeutics, Inc., to bring these reparative cells to patients. Among the early staff members at Osiris was one of Dr. Caplan’s most promising young doctoral students, Scott Bruder Ph.D. At least a couple dozen other companies have been founded on the basis of Caplan’s work.
His more than 400 published papers, 104,000 aggregated citations and 20 patents stands as one of the greatest bodies of work in the history of regenerative medicine.
But, to understand the effect more fully, the reach and enduring importance of Arnold Caplan, which ultimately led to the moniker “father of regenerative medicine,” we turn to Dr. Caplan’s closest friends and colleagues.
Marc Penn, M.D.
“I first met Arnie when I was at the clinic. I got to know him at the Center for Regenerative Medicine. We became really good friends. I’m going to miss him dearly. He was a friend, a mentor, a lot of things to me.
Arnie, I genuinely believe, wanted what was best for each individual. Arnie made me a better scientist, a better Jew, a better father, a better person. He was really a wonderful person to spend time with.
Arnie’s the father of what is currently considered regenerative medicine. Mesenchymal stem cells are the foundation of almost everything. What was great about Arnie is the way he evolved with the science. So many of folks in the field don’t adapt, don’t look at the data.
Arnie was absolutely data-driven. He followed the data, adapted to the data, and didn’t argue against the data—even if he didn’t like it.
There’s no question the field of regenerative medicine is better off because of Arnie. He was its epicenter where everybody who wanted to be in the space could freely collaborate with him and gain the expertise.
Arnie was so much more than what we knew about him as a scientist. Young students at Case who needed advice I would send to him. And he was always very open to talking to them and always really resourceful and insightful to help them.
Arnie moved things forward.
He wanted to see things be successful and funded to the day he died. He wasn’t done, sadly.
He was incredibly satisfied with where he ended up in life and was at peace with all he had achieved.”
Bruno Peault, Ph.D.
“Arnie was very inventive. He had great ideas, frequently ‘out of the box,’ and was always keen to theorize and propose new experiments. He was one of the most thoughtful and creative people I have interacted with in the field of MSCs. He also had a special talent to communicate scientific knowledge to broad audiences.
Arnie had this accurate vision of stem cells, which probably came from his background in developmental biology. He coined the term mesenchymal stem cell. He worked on the emergence of mesodermal tissues in the embryo. By analogy, he proposed that similar mesodermal stem cells are also present in adult tissues.
My original interest and expertise is in hematopoietic stem cells, which have been directly and prospectively identified. It was not the case for MSCs which were produced retrospectively in long-term culture.
We explored this issue and found that MSCs are derived from perivascular cells notably pericytes.
Arnie liked the idea. In all of his presentations, he would talk about the pericyte as the native, tissue resident MSC that can be recruited into tissue regeneration after being shed from blood vessels.
Every time I would see Arnie at a meeting, he would always come with a big smile, and he would say, ‘Bruno, each time I hear you, I hear new things’. That was very nice to hear. But I can say that it was reciprocal. I always learned a lot also from Arnold.”
Rodrigo Somoza Palacios, Ph.D.
“I had read most of his work before I met Arnold Caplan. Arnold is why I’ve been working with MSC since I was an undergraduate student. I was lucky enough to get a scholarship and come from all the way from Chile to attend his three-day short course in 2011. That was the first time I met Arnold in person. He was very interested in me and knew people from Chile including people I knew too. He asked me a lot of questions. He was very nice. I asked him if there was a possibility that I could work with him. He was open to that idea. He never closes any doors.
At that same course in 2011, I met Diego Correa, who was already working with Arnold. He was from Colombia. I actually was born in Colombia.
Diego was working on a project about how MSCs can control bone metastasis. Diego was submitting an NIH funding application for this project. I was lucky enough to finish my Ph.D. at about the time that grant got funded. Arnold and Diego were kind enough to offer me the position of a postdoc in the lab.
Working in Arnold’s lab was a very good experience for me. Arnold met with me probably two, three times a week. Every week he asked me for a new idea. We discussed those ideas, hypothesis, objectives, and how I was planning to do those experiments. Some ideas he hated, some he liked.
Arnold is a big name. Every time I had a meeting with him, before that meeting, I dedicated hours and hours getting prepared. But he always had a question I couldn’t answer. He was always really polite and professional and made me feel like a colleague, not just a postdoc.
He also talked about family. That’s something that really impressed me. Arnold loved his family. Sometimes half of the meeting was about family and travel and other things beyond science. So, I really felt connected to him.
I learned how to achieve scientific excellence from Arnold. I learned how to solve problems. MSCs are not easy to work with. He taught me all the details and tricks to effectively work with MSCs. I also learned how to write grants; we were successful in getting funded.
He had a great impact on me and my career. We were always talking about ideas and experiments. Always he agreed with my ideas, and I agreed with his ideas. I really felt connected with Arnold.
In November, Arnold talked to us about his cancer and the surgery and that it was risky. He was calm about it. He said, ‘I know it’s risky but I’m happy with my life. My family is happy, I’m happy with everything that is happening around me.’
He was very brave.
My goal is to continue Arnold’s legacy. He left our lab with very excited projects going on, how MSCs control cancer metastasis, how MSCs are involved in pain management and, of course, teaching. We are going to continue on that same path.”
David Mooney, Ph.D.
“Dr. Caplan was 20 some years older than me and he was an inspiration for me in terms of the work that he did, the accomplishments he had, his vision, his pioneering research.
As I got to know him personally, I recognized quickly what a great role model he was in terms of how to succeed with all the accomplishments but still continue to engage and interact with others, including the next generation, which he tried to encourage and help.
I had read once that a measure of a true friend is how you feel when you see that person. And every time I would see Arnie, I would smile. He was a good man.
I learned a lot of things from Arnie. Scientifically, he was not afraid to go out on a limb. He would do science very rigorously. He would follow the data and if the data took him in a certain direction, he would follow it and put a stake in the ground and say, this is what I’m finding and this is what I think this means, and here’s how this is going to change how we think about things and how we do things in our field.
Sometimes with all of us, some of our ideas will get refuted by our own work as we go deeper into the science. As time went on, Arnie started saying that these cells mainly work by secreting different molecules that impact the biology around them. That these MSCs are probably not the builders, but rather the ones controlling the other cells.
He went with the science and went with the data and would not get locked in.
Arnie’s work inspired and led to just an incredible amount of research by others. It really is just phenomenal. Arnie had a huge impact. So many people got into this field because of his work. So many people.”
C. Randal Mills, Ph.D.
“When I became the CEO of Osiris Therapeutics, it was a pretty hard time for me. I was a first-time CEO; I was 31 years old and was the seventh CEO the company had hired over the past 4 years. The previous one only lasted 6 weeks! Not great odds.
Right away, all I heard was that I wasn’t going to last very long either, and exhibit A was that Osiris’s founder, Arnold Caplan, hates us.
I sat and thought, ‘Well, that sucks’!
At the time I was trying to figure things out and piece together a business plan. I saw some really phenomenal opportunities for Arnie’s MSCs and the ability to build a great company, but it also required that we make a big cultural leap from Osiris University to Osiris Therapeutics.
But as the plan started coming together, I kept hearing that the guy who founded the company still hates you. I thought, ‘If he’s not on board, how can anyone believe what we are doing?’ So, I just called Arnie out of the blue. And to my shock he answered the phone.
I said, ‘Dr. Kaplan, I’m Randy Mills, and I am the new CEO of Osiris Therapeutics.’ And there’s this uncomfortable pause. So, I just kept talking.
I said, ‘Look, you don’t know me from Adam, but I gotta tell you, I see so much potential in your discoveries. And I think Osiris is gonna become a really, really iconic company in the field of medicine. And I can’t for the life of me figure out why this great company and its founder should be estranged. I’d love to come talk to you about what we’re doing.’
And again, silence. Then Arnold says ‘Yeah, Randy. I’m free next week’.
I said, ‘perfect! I’ll be there.’
It was the winter of 2004 in Cleveland, Ohio, which is not a fun place for a Florida boy. I’m scared to death because Arnold Caplan is not only this guy who founded the company but also the guy who discovered the very principles behind this thing I’ve now fallen in love with. I feel like I’m defending my dissertation again! But instead, I find a man who is so warm and gracious.
He said to me, ‘tell me what you’re going to do.’ And so, I tell him the plan. He says ‘that sounds great. It sounds exactly like what the company needs right now, and what I’ve been hoping Osiris would do. And I can’t wait for you to pay my grandkids college ’cause I’ve given them shares in Osiris!’
So, like, no pressure. And then he took me around and introduced me to everybody, invited me to his lectures, gave me a platform, and over the next decade, lent me his credibility. And became a dear friend.
I’ll never forget that. His grace and generosity forever left an impression on me. We wouldn’t have been successful at Osiris if he had not done that.
Arnold Caplan literally and figuratively put his arm around me, said, ‘You’re onto something, and I’m here for you.’ We lost a lot, and I’m going to miss him.”
Robert Harman, M.D.
“I was a young investigator, 15 years Arnie’s junior, just starting in the field. David Fink, one of Arnie’s good friends, introduced me. I told him ‘I’m hugely honored to meet you and I’m embarrassed with what we’re doing in veterinary medicine without really understanding how these cells function.’
He said, ‘Harman, I know you already and you just have to keep doing this work. It is hugely important.’ Then I said, ‘But Dr. Kaplan, I don’t even understand how these cells work.’
Then he goes, ‘I don’t give an F how they work. I’m telling you they work and go forward. You have the opportunity to create data that we can only dream about on the human side because you’re going to be able to treat lots of patients.’
This was when I had treated 10 horses. And of course he was correct. The next year at ORS, he sees me down the hall and says, ‘So, Harman, was I right?’ And of course he was. We had treated 300 or 400 horses.
Literally everything I did from there forward, had Dr. Caplan’s fingerprint on it.
The thing I admired most about Caplan was his ability to see when things had changed, when there was new data, better data, more insight.
At the beginning, Arnie said here is how these cells work and differentiation was the correct pathway. Five or ten years later, he is lecturing that differentiation is probably not the major mechanism but, rather, these cells are signaling drugstores. And we started looking at how cytokines would be produced and that, wait a minute, maybe they’re not even the stem cells, maybe they’re getting eaten by macrophages. And the macrophages are tissue resident and begin to express the same phenotype as the stem cells.
I think of the fourth generation of these insights from Arnie’s work is not a change in the paradigm, but the additions of pain and antibacterial and antiviral effects of these cells.
Each one of these changes in the view of what these cells do had a profound impact on how we developed veterinary cellular therapies.
I would call Arnie periodically and say, we just used cellular therapies with a northern white rhino, we just did a giraffe. Now we’re working with marine mammals, we’ve done turtles. And we would talk about it and if there’s one thing in my entire career in regenerative medicine that stands out, it is how these cells work across all these species. It’s amazing. Amphibians, reptiles. I did a condor a couple months ago, birds, dolphins, orcas. They all respond the same way.
Arnie’s views were constantly evolving. I must’ve listened to his MSC talk a hundred times over the last 15 years. I know people would just roll their eyes and go; it’s the Caplan talk again. But it never was. Arnie’s talk always had a little evolution. If you paid attention, it was profound.
Arne was larger than life, strong and a little bit stubborn. Finally, he had more clinical compassion than anybody I could ever imagine. I mean, he just cared about the patients and getting this technology. I hope nobody forgets. He impacted so many of us.”
Steven Goldstein, M.D.
“Arnie was always present. Besides being prolific in publishing, he was prolific in being present in the scientific community. He was on the podium, in the audience, at the meetings and he was nonstop.
Arnie Caplan was relentless in terms of making sure that he provided the findings of his science, his perspectives, his predictions of how mechanisms worked. Although he was immensely confident, he wasn’t afraid of being wrong.
He was tenacious. If he was still here, he would be working on new grants and ideas. He would be traveling the world lecturing, and he would be pushing entrepreneurial limits.
Arnie always knew he wanted he was always ‘in charge’. He had a kind of fearlessness which, I think, influenced how he did science—with tenacity and fearlessness.
Perhaps his most significant contributions related to regenerative healing and regenerative medicine. It was this work that we shared in common and resulted in collaborations. His work identifying the role of mesenchymal stem cells and the interactions among the multiple factors associated with the cascade of events directing tissue formation, repair and regeneration influenced all in the field. It was critical to my own work investigating the interplay between mechanical and biologic regulators of bone metabolism.
Our approach to life science and family were so similar that we sort of had a natural and very personal connection. I didn’t have enough time, personal time, with Arnie. We always tried to get together, get our families together. That remains far too unfulfilled. My last wish to Arnie was for him to be at peace. My wish was for more time with him.”
Stan Gerson, M.D.
“I think the field has lost its convener and synthesizer.
He was infectious in his collaborative engagements. We had a celebration of Arnie’s 50 years at Case four or five years ago and the number of international colleagues who flew in on their own volition to be there was really quite astonishing.
Arnie’s aptitude for engagement and attentiveness was quite remarkable. Which wasn’t just a social engagement, he would connect people in science and give them something new to think about.
Arnold Caplan was a simulant for discovery.
Arnie’s fundamental intellect was to broadly reassess his own inventiveness and perceptions and to be as inclusive, as engaging as he could to build a comprehensive model.
Arnie could also drive everybody crazy because every time you talked to him, he’d have a new idea that he was just as confident of as he was of the prior rule.
Within the first few months of my joining Case in 1983 I heard Arnie talking about cartilage in eggshells or the ceramic matrix of eggshells, something like that. I was fascinated with his approach and style. I’m a hematopoietic stem cell person. Always have been. My area of interest is DNA repair of hematopoietic stem cells.
My involvement with Arnie was in the therapeutic application of these cells. What do these cells do? How do they contribute to the physiology of the body of the tissue? Can they be manipulated, utilized, resurfaced, repurposed for a therapeutic value?
Thirty years ago, we showed that if you stimulated mesenchymal stem cells, they would produce 30 or 40 massive increases in cytokines. Refining that crude observation from 30 years ago was frankly something Arnie spent 30 years studying. And Arnie really pushed hard on the breakthrough versus the incremental science.”
Scott Bruder Ph.D.
“That first week I was in Arnie’s lab in 1984, he said, ‘give me all the papers and everything that you wrote as an undergraduate for your thesis.’ So, I brought it in and gave it to him the next morning. He came back the next day. He read it all that night. He’s got good technical questions for me, and then he asked me something…something that he has since always asked me…the question that was the turning point in our relationship…he asked me: ‘What’s the next experiment? Tell me the experiment you want to do. And what’s the next experiment after that?’
In other words, Arnie was telling me to design my investigation and experiments in such a way that, no matter the outcome you learned something.
My dad died 3 years before I entered Arnie’s lab. I was 19 years old. Arnie was very paternalistic, and I viewed him as my scientific father and in many ways a surrogate father. I became very close with the whole family, Bonnie and Aaron and Rachel. He was in the restaurant the night I proposed to my wife. They sent over a bottle of champagne. He celebrated my wedding and has been a part of my children’s lives growing up. He was at both of their Bat Mitzvahs, and Hannah’s wedding last year.
The thing that made him a good scientist is he was always asking questions. He wanted to understand the next implication of the observation and how that tied to other things that some people might not find an affiliation or association with. Things like immunology, and then what he’d learned about embryology and cell therapies.
At the time that we first identified MSCs, everybody thought we were full of shit. Many serious scientists didn’t believe us, until they eventually reproduced the results, and then they became converts. Which is another interesting story because Arnie had this nickname when I started in the lab. He was the ‘Full of Bull’ Professor. He would say things that people thought were preposterous. Eventually though, most of it turned out to be true.
Another thing that made him a very good scientist was—and it’s a double-edged sword here—he was very dogmatic about things. This is the way he was, sometimes to a fault, but eventually, when presented with compelling data, he had the humility to say, ‘I was wrong.’
He came to the view that MSCs were not stem cells in the classical way of hematopoietic stem cells. So, he began calling them Medicinal Signaling Cells, because the way that they work, and he pleaded with everyone to STOP calling them stem cells.
The last time I saw Arnie was at his birthday, January 5. His caregivers at the hospice center brought him to a common space, where his closest friends and family waited to share their parting thoughts with him. I waited patiently until the end because Bonnie, his wife, said ‘I want you to have some extra time there, because you’re ‘the favorite son.’
I approached him and took his hand. One of the things that I asked him in our last moments together after 4 decades of weekly discussions was, ‘Boss, what do you want me to do next?’ And he said, ‘Help everybody bring products to market. You can do it.’ Then I said to him. I am just so happy to see that you had an incredible 82-year run, and I’ve been blessed to be part of it for the last 40 years. You’ve travelled the world. You’ve impacted science.’
Then Arnie said., and this is the part that chokes me up, he said, ‘It’s been an incredible role reversal. I was your teacher for the first 20 years, and you became my teacher the last 20 years. Help get this science into people!’ Then he said, ‘so keep developing products. Get your clients, get your peers, and get your colleagues aligned to impact healthcare, help them get these things into market.’
But that was our relationship.
What’s the next experiment, and the one after that? Why are you doing that experiment? The other thing he used to say is: ‘Do the hard experiment first. And try, you know, try to do the heroic things. Make a difference.’ I plan to honor his wishes with as many people and technologies as possible.”
Cheryl Blanchard, Ph.D.
“I first met Arnie when I was the Chief Scientific Officer at Zimmer years ago. He was what I would consider to be the quintessential professor—challenged thinking and asking questions. Arnie was a real role model for me about how to just keep asking the right questions. What we do is hard. There are no easy answers.
He had a way of tying science to business. He understood that at the end of the day, patients get therapies because a business develops them. I think he saw how that ecosystem worked very early on.
I don’t know that Arnie ever got his full credit due for the science he pushed forward that frankly resulted in so many therapies used ubiquitously today. People kind of tend to forget that there was a foundation laid for our clinical success today.
The seminal work that Arnie did around mesenchymal stem cells had an impact across many therapeutic areas. He really got clinicians and researchers thinking about what biologics could mean in the field of orthopedics.
I think the biggest thing he did for me is he would listen, go through my thinking with me. He had this way of saying: ‘Let’s ask a whole bunch of questions, you don’t have to get four answers out of your mouth before we’ve had a chance to think about things.’
Arnie was a very giving person. He viewed it as his place on earth to give and challenge, and so he did.”
Anthony Atala, Ph.D.
“Arnold Caplan and I met several decades ago. He was an amazingly warm, charismatic individual—truly one of a kind. We formed an instant and wonderful life-long friendship. Our mutual scientific interest involved stem cells and their potential.
Arnie’s groundbreaking work with bone marrow derived mesenchymal stem cells (MSCs) formed the basis for our own work, enabling us to find highly multipotent stem cells in amniotic fluid and placenta which can be directed to all three germ layers, endodermal, mesenchymal, and mesodermal. We had ongoing discussions about different stem cells.
Every time I’d see Arnie, he’d have something new. He’d say, ‘I’m working with these cells and now they’re doing this. I’m working with this now.’ He was always advancing the field. He was not satisfied with the status quo. He just wanted to keep moving forward.
Over time, new discoveries are made and our understanding in science advances. Arnie saw the stem cell field evolve and felt a personal responsibility to advocate for the most current science. He highlighted a paradigm-shift regarding MSCs, proposing a new nomenclature of Medicinal Signaling Cells instead of Mesenchymal Stem Cells, further defining their expansive potential.
The body of work he accomplished in his lifetime was monumental.”
