This transcript has been edited for clarity.
welcome Impact FactorEach week we bring you commentary on new medical research. I'm Dr. F. Perry Wilson from the Yale School of Medicine.
Here's the pitch: You've heard of stem cells, right? They're amazing cells that can turn into any type of cell you need, depending on where you put them. They can become blood vessels, brain cells, cartilage-building cells. And in your knee. Osteoarthritis It's just bone to bone. What I'm going to do is inject stem cells into the knee, and they'll take hold there and build more cartilage and fix the pain. Insurance won't cover it. It'll cost, like, $5,000.
The proposal is, A $35 Billion Industry And stem cell clinics are popping up all over the country, offering very big promises.
However, when you look at the actual trial data of stem cell therapy for diseases such as osteoarthritis, you will be very disappointed. Here is a study that shows this: Injections are less effective than steroid injectionswhich is about 100 times cheaper and, frankly, doesn't work as well on its own.
In fact, we might conclude that these injections are, as my kids would say, at best pretty half-baked and at worst just another variation of pseudoscientific nonsense. And this week, a new study It brought me even closer to that pseudoscientific interpretation.
I just want to define some terminology here: The research that I'm reporting on this week is not about using stem cells in the context of bone marrow transplants or anything like that. This is actually about outpatient stem cell procedures that are done in a doctor's office to relieve a variety of pains and ailments.
Patients typically visit a “regenerative medicine” clinic, are examined, and given a small amount of Liposuction Fat is harvested from the abdomen or, less commonly, bone marrow aspirate. Both tissue sources are thought to be rich in stem cells and are used interchangeably. The aspirated tissue is not processed (the FDA has not approved the use of cultured cells in these procedures), so you are essentially aspirating fat from the abdomen and injecting it into the knee. That's the procedure.
So you have to ask yourself right away: “Did I get stem cells?” Obviously, I got more than just stem cells. I got fat cells, I got maybe blood or plasma, and a variety of proteins and other substances.
Maybe the right question is, how many stem cells did I get? And this study Scientific advancestake off.
The researchers enrolled 21 subjects and followed the same procedure used in hundreds of clinics around the world: They aspirated bone marrow and abdominal fat, which are supposedly interchangeable sources of stem cells, but instead of injecting them into the knee, they pumped them into the most sophisticated analytical equipment available in modern molecular biology laboratories.
Let’s start with the first and biggest question: If you inject abdominal fat into your knee, how many of them will become stem cells?
It turns out there are several standard ways to define whether a particular cell is a stem cell or not, based on markers that appear on the cell surface. A unique combination of different markers gives us detailed information about what kind of cell it is. One combination represents a T-helper cell, another represents a fibrocyte, and what we're looking for are mesenchymal stem cells that have this particular combination of surface markers.
The researchers then looked for these stem cells in the bone marrow slurry, filtering the data, and found 3.5.
Not 3.5 million, not 3,500, but 3.5 cells per sample.
One of the samples contained no stem cells at all, and in the most concentrated sample, 0.017% of the cells identified were stem cells—a number so small that the researchers couldn't even rule out the possibility that all of these cells were simply false positives.
Fat samples fared slightly better, with an average of 1.7 percent of the cells identified appearing to be stem cells, but when they were examined they found that the cells had a range of sizes and textures and were not a uniform area of cells.
“This also suggests a high false positive rate. Perhaps these samples essentially do not contain stem cells. Or perhaps stem cells are just misdefined. The authors suggest the latter and decided to try a different method to find the elusive stem cells.
This is where tissue transcriptomics comes in. Here, we analyze the RNA of cells taken from fat or bone marrow. Instead of asking what the surface markers of the cells are, we ask a more fundamental question: What are these cells doing? What are they producing?
The answer, of course, is “a lot.” But by measuring all of these things, we can plot how similar a cell is behaving to other cells, like this: Each dot here is a cell. The black dots are bone marrow cells, the pink dots are fat cells.
First, note that pink and black don't mix, which means that bone marrow cells and fat cells are very different and not interchangeable as has been suggested in the past.
And look at the little red box on the bottom right: There are just a few cells there that appear to be stem cells (they're all black, by the way). So stem cells are only found in bone marrow, not in fat, but they're buried in a sea of cells that perform other functions.
In another experiment, we enriched the slurry with cultured stem cells (the real thing, the gold standard), which are not available at this time because they are not FDA approved to treat knee pain or anything else. You can see lots of blue stem cells, close to the bone marrow stem cells scattered throughout, but not overlapping.
Looking at this, I would argue that if these injections work (a big “if”), it won't work because of the stem cells – there's a whole bunch of other things out there.
So far, we've only talked about cells. When you stick a needle in a layer of fat and aspirate it, you don't just get cells. You also get a lot of proteins. Researchers have characterized all of the proteins in fat and bone marrow aspirates.
Notably, only 10 of the proteins detected had important immune-modulating functions that could aid in joint healing, and only 4 of the 10 were detected in both fat and bone marrow aspirates.
This is a very detailed paper, Fully interactive website I agree, and encourage anyone interested to look into it further. But the point I want to make is that we essentially have no idea how these “stem cell” injections work, or if they even work at all. The reason is that when you inject a variety of different substances into a joint – cells, proteins, fluids, cytokines – you don't know which substances are biologically active. Perhaps the reason the clinical trial data for these treatments is so inconsistent is that the substances you inject can vary widely depending on where you get them.
I don't know if or how these injections work. teeth What is clear to me is that marketing “Stem cell therapy” and “regenerative medicine” definitely work. It's a wonderfully simple story of taking your own body's cells and healing yourself. No drugs or surgery required. Just a little fat, a little hope, and $5,000 that insurance won't cover.
Cost aside, the idea is great. But let's be honest: if we really believe that stem cells are the magic bullet here, we need to isolate them before injecting them, or ideally, culture them until we have enough of them to actually have an effect. Neither isolating nor culturing cells for this purpose is currently FDA-approved. To get approval, someone would need to show that the preparation actually works. That's not hard at all, if the marketing is right. Right?
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University. His science communication articles can be found on Huffington Post, NPR, and Medscape. He tweeted: Perry WilsonAnd his book, How drugs work and when they don't, is now available.
