Maxine is doing it. Tiny Timon is doing it too. Nash is about to start and Sushi the pug is now 鈥減ain-free and thriving.鈥� At a certain age, seemingly every dog on Instagram starts embracing stem cells.
The veterinary clinics that offer this service call it 鈥渋nnovative鈥� and 鈥減roven,鈥� with benefits lasting 鈥渕any years.鈥� If you are to believe your feed, the fountain of youth has finally been found and its water is teeming with stem cells.
滨鈥檝别听written before聽about how stem cells are ripped from the lab bench and put inside a shiny commercial case for human customers eager to get a taste of regenerative medicine. But many of these customers have pets, and when disease strikes or old age sets in, they will hear the siren song of stem cell therapies in the form of cat purrs and dog barks on Instagram.
These interventions still have little evidence behind them, which may anger the people who have been seduced by their promise for decades. Why is science so slow to deliver on the healing potential of stem cells?
Mesenchymal stem cells: the flavour of the decade
It鈥檚 useful to think of stem cells as babies. The cells that make up our body have special shapes and functions: we have lung cells, and muscle cells, and white blood cells. But these very specific cells originate from earlier cells known as stem cells. Like a baby, a stem cell has the potential to differentiate itself and specialize in order to perform a specific job. Another property they have is the ability to self-renew indefinitely.
You may remember the political debates of 2000s over聽embryonic stem cells.聽They carried a lot of promise because they could become any cell the body could need, but they required the destruction of embryos in order to be initially harvested. Their use as treatments inside the body also came with risks, such as the immune system rejecting them and their potential to turn cancerous.
You may also remember the news in 2006 that Japanese researchers had managed to take adult, differentiated cells and, by turning on a few key genes inside of them, revert them back to a type of stem cell. They are known as聽induced pluripotent stem cells, and while they forego the need for embryos, they cannot turn into any cell our body needs. Their potential is more limited, and they still carry the risk of giving the patient cancer.
We finally arrive at聽mesenchymal stem cells, which is what pet influencers on Instagram are receiving. They are a subset of stem cells, naturally present in the body, which can come in to replace injured or diseased tissue by transforming themselves into bone, cartilage, ligament, tendon, fat, skin, muscle, or connective tissue.
Unlike the previous two categories of stem cells, mesenchymal stem cells appear to be quite safe when they are injected inside the body as a treatment. There are still theoretical risks, and research studies almost never follow up with their participants long enough to catch side effects that might appear six months later or more. But because they can be collected from many places in the body鈥攎ost commonly fat and bone marrow鈥攂oth researchers and entrepreneurs have now pivoted to them.
Two technical words you will encounter in this area are 鈥渁utologous鈥� and 鈥渁llogeneic.鈥� An autologous stem cell transplant means that the stem cells come from you鈥斺�渁uto鈥� is Greek for 鈥渟elf鈥濃�攕o the stem cell donor and recipient are the same person. In pets, autologous treatments are much more common, but they require anesthesia and surgery to collect the cells from the animal. We also know that the quality of stem cells in older animals is聽.
An allogeneic transplant comes from a donor other than the recipient鈥斺�渁llos鈥� is Greek for 鈥渙ther.鈥� Allogeneic products would be more convenient and akin to drugs: made from single sources, standardized and quality controlled. In rare cases, scientists will perform xenogeneic stem cell transplants, meaning that the donor comes from a different species than the recipient.
As to whether or not they work as treatments in companion animals, what the scientific literature still says to this day is that they are 鈥減romising.鈥�
Canine osteoarthritis
The best evidence we currently have for stem cell therapies in pets鈥攅vidence that, to be clear, is far from conclusive鈥攊s in dogs with osteoarthritis, and the reason is quite interesting.
Osteoarthritis affects cartilage in our articulations, and because this cartilage is聽, it does not heal easily. Over time, a painful, degenerative condition known as osteoarthritis can set in. In humans, its聽聽include aging, obesity, direct injury to the joint, and genetic factors, with the knee being the most commonly affected articulation. Its progression cannot be stopped at the moment, so doctors will prescribe pain medication, physical therapy and, in serious cases, joint replacement surgeries. Better interventions require research, but on what can we research osteoarthritis?
It turns out that dogs are really good models of the disease. It can be induced in laboratory dogs, but dogs also naturally develop osteoarthritis: in fact, about聽聽will get diagnosed with the disease. Unlike in humans, though, where osteoarthritis often sets in even though the articulation has never been injured, osteoarthritis in dogs is聽.
The use of dogs to conduct research into treatments for osteoarthritis in humans has thus led to interventions also being tried in the dogs themselves, since many dog owners are desperate for solutions to this degenerative condition. The studies done on the use of stem cells in dogs to treat osteoarthritis usually report significant improvements, which is encouraging, but there is聽.
The number of animals being treated in each study is usually very small: in fact, many reports are little more than documented anecdotes. The use of control groups鈥攚here a group of dogs is given, let鈥檚 say, a saline injection to rule out improvement due to factors that have nothing to do with the stem cells themselves鈥攊s uncommon, because owners often don鈥檛 want to risk their dog not receiving an actual treatment. Assessing pain in humans is already challenging due to its subjectivity; dogs can鈥檛 communicate their pain, so assessment is often done by the owner, who wants the treatment to work. Follow-ups are short, so long-term benefits are unknown. Importantly, the amount of stem cells injected varies from study to study, from 1 million to over 100 million, and the cells are rarely studied in the lab prior to injection to know exactly what has been extracted. Very few researchers actually check the treated joint to make sure the cells have differentiated and integrated, and we know that聽, once administered, are lost due to inflammation, stress, or lack of oxygen at the site of injection. Doses have to be high enough to compensate for this loss but how high when higher doses mean increasing the odds, however theoretical, of causing cancer?
When it comes to mesenchymal stem cells treating conditions other than osteoarthritis, and their use in cats or horses, the evidence is so thin at the moment that the word 鈥減romising鈥� is still all we can muster.
Stem cells are not new. The first stem cell transplant done in humans dates back to聽, with a much cruder bone marrow transfusion preceding it in 1939. These stem cell grafts have become common in the treatment of many blood and bone marrow cancers which, to this day, remain some of the very few evidence-based, clinically approved applications of a stem cell therapy. And our knowledge has changed over the decades: we used to think these cells were useful because they became the type of cell needed to fix an ailing joint, for instance, but we now know that their main benefit is in secreting molecules that play聽.
Yet, despite a clearer understanding and many decades spent working on them, proven applications are thin on the ground.
Where鈥檚 my jetpack?聽
I reached out to friend of the Office, Timothy Caulfield, a University of Alberta professor and research director of the Health Law Institute, who has kept a close eye on developments in the field of stem cells while denouncing undue hype. How can we have 鈥渄ecades of promises,鈥� as he put it to me, with so little to show for it? In part because of embryonic stem cell research, which stirred up a controversy that slowed down developments. And because stem cells are easily marketable as having immense healing potential, the appeal of skipping the research to sell empty promises straight to consumers can be hard to ignore.
In the veterinary space, all of the problems of human research get magnified. Brennen McKenzie is a veterinarian who runs the聽聽website and who has reported on the evidence behind stem cells in companion animals聽. In an email, he told me he doesn鈥檛 think the limited evidence is likely due to stem cells not working. Rather, money is hard to come by. No significant government funding goes to veterinary medicine, which leaves the latter dependent on limited, private sources of financing which expect significant returns on investment. But given that the pet market is smaller than the human one, private investments are smaller too.
Studies that end up getting funded can be hard to compare to each other: researchers use different doses of stem cells extracted in various ways to treat different conditions, leading to a basket of apples and oranges that don鈥檛 have much in common.
We also see a lack of regulatory oversight which, ironically, leads to a disinterest in proper research. The regulatory agencies of most countries in the world do not strictly supervise stem-cell-based therapies aimed at pets. In the United States, the Food and Drug Administration (FDA) should in theory ensure that these interventions are tested and approved according to strict criteria, but as McKenzie tells me, it has long lacked both funding and political support to do this. Mass firings of staff at American regulatory agencies and RFK Jr鈥檚 embrace of pseudoscience are bound to worsen the situation, in my opinion.
Instead of strict regulation, the FDA exercises 鈥渆nforcement discretion鈥� to such an extent that companies can make and market these therapies without appropriate testing beforehand. 鈥淲hy put the time and money into appropriate clinical trials,鈥� McKenzie asked me rhetorically, 鈥渋f you can go ahead and sell your product and make efficacy claims without them?鈥�
The much-vaunted replications which we hold dear in science are rare in this field due to proprietary information, competing products, and limited funding. We thus end up with lagging, scattershot research and a bevy of unproven commercial products.聽
Stem cell therapies are not alone in seeing their promises marketed directly to consumers while the evidence mostly fails to materialize. Hype around the聽microbiome, cold laser therapy (also known as聽photobiomodulation), and聽epigenetics聽has likewise been successfully packaged by marketing gurus.
The good news about mesenchymal stem cell interventions in pets is that they appear to be quite safe. The less-good news is that long-term follow-up is lacking, so we don鈥檛 know for sure. We thought they could escape detection by the immune system and thus rejection, but聽. It may very well be that, over time, the immune system聽诲辞别蝉听perceive them as foreign.
At this point, stem cells to treat osteoarthritis in dogs may help, but you should know that you are essentially signing up for an聽n-of-1 experiment. Will your dog actually benefit or will you simply see what you want to see?
Take-home message:
- The benefits of mesenchymal stem cell therapies in pets have still not been proven by rigorous scientific studies, but limited evidence suggests they are usually safe
- The best evidence so far is in the use of stem cells to treat dogs with osteoarthritis, yet even those studies have major limitations
- Regulatory agencies typically do not closely monitor stem cell treatments for companion animals, which means that companies can sell these interventions without good scientific evidence behind them
