Mesenchymal stem cells play a key role in orthopedics because of their differentiation potential and, more importantly, their immunomodulatory effects on healing tissues.
Video Highlights
Many types of stem cells exist, but contemporary orthopedic discussions focus almost exclusively on adult stem cells, particularly mesenchymal stem cells (MSCs).
Among adult stem cells, MSCs are highlighted for their relevance to orthopedic tissues because they can differentiate into bone, cartilage, tendon, ligament and fat. Their developmental pathway is influenced by the local cellular and environmental “niche,” including factors like oxygen levels and pH.
Although MSCs were historically viewed mainly as building blocks for new tissue, current interest centers less on direct tissue replacement and more on how MSCs influence the local environment. This includes their ability to promote angiogenesis and coordinate repair processes.
Excitingly, MSCs can also activate local healing responses, recruit additional cells and direct cellular behavior in injured tissue. They exhibit anti‑inflammatory, anti‑fibrotic, anti‑bacterial and anti‑apoptotic properties, which may help limit secondary tissue damage following injury and support a more favorable healing environment.
With stem cell therapies drawing attention in professional sports for treating injuries, orthopedic surgeons are increasingly fielding patient questions about these treatments. Yet many clinicians have had limited formal training in stem cell biology.
In this video, Dr. Patrick McCulloch, professor of clinical orthopedic surgery at Houston Methodist Hospital, reviews the foundational science most relevant to orthopedic practice. He clarifies how mesenchymal stem cells (MSCs) differ from other stem cell types and why they remain the primary focus in current orthopedic applications. The discussion emphasizes mechanisms of action that matter clinically rather than speculative regenerative claims.
Article Transcript
00:00–00:30 Hello, my name is Patrick McCulloch, and Im a professor of clinical orthopedic surgery at Houston Methodist Hospital. Today I’m going to be discussing the use of mesenchymal stem cells in orthopedic surgery. So what are stem cells? So every time we're in clinic, we have patients who come in and ask us about stem cells. They want to know what the latest is and what the state of the science is. But for a lot of us, we don't have a lot of training or expertise in stem cells. So I want to go over some of the basic facts.
00:30–01:00 So what makes a stem cell? So two properties make a stem cell. The ability to self renew which means from one stem cell to be able to divide and have two, and then to continue dividing, and then you can have more and more. So this process can keep going. And this is called self-renewal. And the amount of time that it takes to go to each level we call the doubling time. So if those stem cells are very active then the doubling time will be low, meaning you can get a large number in a short amount of time.
01:00–01:30 The second feature is their ability to differentiate. So a stem cell can start as a stem cell, but when it divides you may get a stem cell and a progenitor cell that looks different. And this progenitor cell can then go on to make various different tissues. So stem cells have the ability to turn into multiple different tissues, which makes them sort of magical, and why there's a lot of interest in their potential for therapeutics.
01:30–02:00 So there are different types of stem cells, so this is an important point. So first we have embryonic stem cells. So those come from a human embryo. So when you have an embryo of a developing human it's basically a ball of cells, and the inner cell mass right here is where you can harvest embryonic stem cells.
02:00–02:30 And those cells, just like when you have an early embryo and it has to become a human, so it has to develop into bones and muscles and other tissues, well, these cells have that ability. So this is a little bit of less interest from a therapeutic standpoint at this point because of the fact that there are some regulatory, legal or ethical issues revolving around the use of human embryos.
02:30–03:00 for research or for therapy. This next category that we call IPCs, or Induced Pluripotent Cells, this is a really interesting thing. So this is where you can take actually an adult cell, but it doesn't have to be a stem cell, it can be a differentiated cell of some kind. So maybe even just a skin cell, and then you can take that cell and inject four factors into it.
03:00–03:30 They're called transcription factors. And you can make that cell reset and become a stem cell. And so for this to happen this was discovered by Yamanaka in Japan, and Gurdon in England for which they won the Nobel Prize in 2012. The tricky part about this is in order to get those four Yamanaka factors in there, typically that's done with a viral vector to introduce those transcription factors,
03:30–04:00 and there's concerns about using that in humans as to whether perhaps some of the viral DNA could get incorporated and that could be an issue. So while that has some really interesting promise, what we're mostly talking about when we're thinking about stem cell therapies these days are adult stem cells. And then there are two different types.
04:00–04:30 There's the hematopoietic stem cells. And the mesenchymal stem cells. So hematopoietic stem cells are ones that are in the bone marrow. They're also in the blood. And these are being used now FDA approved for clinical purposes. So for example, a stem cell treatment for someone with a blood cancer. So if you have a blood cancer, well then we can take hematopoietic stem cells,
04:30–05:00 and then we can by giving chemotherapy knock out all the disease cells and have them all replaced by growing a whole new colony of all the blood cells that you need. So that's what hematopoietic cells do. Mesenchymal stem cells are the ones we're talking about in orthopedics, because those can make up most of the other tissues that we need for orthopedic conditions.
05:00–05:30 And when we look at a stem cell we talk about its lineage. So initially we have a cell, and this may be our stem cell, and when that cell divides we can have more and more of those. And those can divide. And we get what are called progenitor cells. And these progenitor cells then may follow along a different pathway to become all of these different tissues.
05:30–06:00 So, MSCs can become bone, cartilage, fat, tendon, ligament. So basically everything that we're interested in in orthopedics, the MSCs have the ability to become those tissues. As to which course they go down, well, that's directed by a couple things that collectively we call the niche.
06:00–06:30 So the niche may be the cells surrounding it that help direct it to go to where it needs to go, or to make it differentiate into what tissue it needs to be. The niche is not just cells though. It's also the environment. So it's a combination of both the local cells and environmental factors. So for example, a particular early stage progenitor cell,
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06:30–07:00 well if the environment is one that has more oxygen rather than less oxygen, well that may make it want to go more towards bone and less oxygen, more towards cartilage. Or what is the pH of that environment? And that helps to dictate how they differentiate. So we already talked about the MSC properties that, hey, they can self regenerate. So you have this pool of cells that are just waiting to do something, and they can reproduce themselves.
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07:00–07:30 We talked about the fact that they can differentiate into basically all of the tissues that we need for our musculoskeletal system. And so that's what generated the most interest. And in fact, Arnold Caplan, was considered the father of mesenchymal stem cells, and he was working on these in the 1980s, and in 1991, he wrote a seminal paper that suggested that these may be of use for therapeutic purposes.
07:30–08:00 So he's the father of it. And a lot of the thought was that maybe it's because of their differentiation. However, we now think about them a little bit differently. So it may be the fact that they can turn into those tissues, it may be the fact that they can help to create new blood vessels. So new blood vessels are responsible for helping to maintain tissues, helping to repair tissues or even regenerate them. But our main focus these days is really on their immunomodulatory capacity.
However, we now think about them
08:00–08:30 So what do they do to the local environment and to the other cells? So, one is they can activate local cells to start a healing response. They can recruit new cells into the area, which can add to the response that we get.
08:30–09:00 And then they can direct what those cells do. And when they're directing them, they have lots of properties which are really important. So, one is anti-inflammatory. Another is anti fibrotic.
09:00–09:30 to be anti-bacterial. And the last one that I would mention is anti-apoptotic. So apoptosis refers to programmed cell death. So in the case of an injury you have inflammation, and that actually causes some of the local cells to undergo apoptosis or to die. And the stem cells can actually stop the apoptosis process.
09:30–10:00 So in this talk we've talked about what MSCs are, what they do, what defines them. And I think this is really helpful for orthopedic surgeons to know what we're talking about when we're talking about autologous cells or allogeneic cells, whether we're talking about embryonic or adult mesenchymal cells. So this is the end of the first part of the talk.
10:00–10:30 we're going to talk about different sources of stem cells and what we've done with them in the lab to help get them ready for putting them back in patients as true cell therapies. Thank you.