Stem cell therapies have the potential to treat many conditions, but so far there’s little proof that they do. Even so, clinics around the world offer stem cell-based treatments for a host of medical problems. New research warns that some of these treatments might not be effective and can, in fact, cause harm — sometimes many years down the line.
A report in the journal CMAJ details the case of a 38-year-old man who developed a benign tumor on his spinal cord that his doctors linked to an experimental stem cell treatment he received 12 years earlier. They said his case highlights the hazards of unproven stem cell-based therapies, as well as the length of time it can take for serious problems to arise.
“The worst-case scenario is not necessarily that [stem cell therapy] doesn’t work,” said Dr. Nanette Hache, one of the man’s physicians and a professor of radiology at Memorial University of Newfoundland. “There can be other complications, such as tumor formation.”
When the man was 20 years old, he injured his spine during a trampoline accident. Even after surgery and rehabilitation, he was left with some paralysis in his arms and severe paralysis in his legs and torso. At age 26, he underwent a stem cell procedure in Portugal that involved transplanting cells from inside his nose onto the spot of his spinal cord injury. The goal was to alleviate his pain and perhaps even help him walk again.
For people who have run out of conventional options, the choice to try something that hasn’t been solidly tested could seem low risk and high reward.
“You can imagine if you had this type of injury you’d want to research it and see if there was anything out there that could potentially help you,” Hache said. “Even if wasn’t mainstream medicine.”
Instead of relief, the man experienced additional pain and never gained extra use of his arms or legs. Twelve years later, he was referred to Hache and her colleagues after he noticed decreasing function in his arms and bladder over the previous three or four years.
The team identified a large mass on the upper part of his spine. When they analyzed samples taken from the mass, they matched the cells in the samples to the type of cells that had been transplanted into his spinal cord: cells from the olfactory mucosa — the mucous membrane that lines the nasal cavities.
Hache and her colleagues surgically removed part of the man’s tumor but could not remove it entirely without risking further injury. While the tumor isn’t considered cancerous, the team is using radiation to help slow its regrowth.
Cells from inside the nose may seem like a strange choice for a spinal graft, but the olfactory mucosa is easy to access and contains cells that can differentiate to form various cell types. Scientists are studying their use in stem cell transplants, and there is some evidence to support the idea that this approach could help patients recover from spinal cord injuries.
The procedure has shown some promise in animal models, and the team in Portugal that performed the man’s transplant published a pilot study of the procedure in 20 individuals with spinal cord injuries. They reported improvements in about half of them. Other studies had similar findings.
But as Hache and her colleagues point out in the CMAJ report, these studies examined a small number of patients and were neither randomized nor blinded. Given the lack of controls, it is difficult to know whether any improvements were due to the transplant or to the rehabilitation that patients underwent after surgery.
University of Minnesota bioethicist Leigh Turner said this case demonstrates what can happen when techniques and cells that aren’t fully understood are used to treat disease.
“If you put the wrong kinds of cells in the wrong location in the human body, there can be unwanted effects that just aren’t clear at the time,” he said. “And they aren’t necessarily picked up in preclinical research or with animal models.”
Some stem cell-based therapies, like bone marrow transplants, are known to be relatively safe and effective. For many other stem cell approaches though, Hache and others believe that more research is needed before they are offered to patients.
The patient she treated joins what may be a growing group of people who experience serious complications from stem cell transplants. A 2018 analysis reported 35 cases of complications or deaths following unproven stem cell-based treatments, including loss of vision, infections, cardiovascular complications, and cancer. While the researchers acknowledged that some of these problems could have been caused by the implant procedure, others “are likely the direct result of the yet unproven treatments using stem cells,” they wrote.
Cases like this sometimes bring up concerns about “stem cell tourism,” in which people travel to different countries for operations and treatments that aren’t available or accessible in their home countries.
While this patient did travel to Portugal, Turner, who has long voiced criticism of clinics that offer unproven treatments, said his case is complicated.
“It’s not quite as simple as individuals from Canada, United States, and elsewhere going to some kind of dodgy, obscure clinic in the far ends of the world,” Turner said, pointing out that the doctor who performed the transplant has published in peer-reviewed journals and appears to have observed few adverse effects in the patients he and his team treated and tracked.
Stem cell-based therapies are available in North America, and the United States actually has the largest number of stem cell clinics in the world. But invasive procedures like this tend to happen more often outside the U.S. and Canada, Hache said.
There are several known cases in which individuals developed similar spinal tumors after undergoing stem cell transplants using olfactory mucosal cells. At least one of them received a stem cell transplant from the same medical team in Portugal as the man Hache is now treating. In its pilot study, the Portuguese team followed patients after their surgery for an average of about 28 months. For Hache’s patient, that would not have been long enough to detect the mass that eventually grew on his spine.
“It’s such a slow process for these tumors to grow,” Hache said. “The latency period can be years and in his case was greater than seven years.”
Given the longer time frame needed for such side effects to show, similar cases could arise down the line. There could also be patients who are experiencing long-term effects that haven’t led to case reports.
“Are there other individuals walking around who have these complications and they just didn’t make it into the academic literature?” Turner said. “I think it’s a possibility. It may be that from a long-term perspective, the safety profile is different. We need to be aware of the possibility of long-term complications.”
Stem cell clinics in North America and around the world have been criticized for advertising unproven therapies to patients.
“Because people are vulnerable and because they’ve got this illness and they’re desperate for a cure of some sort, they’re willing to take risks,” Hache said. “And they pay a good sum of money to have these treatments done.”
The case report notes that olfactory mucosal transplants cost about $50,000, which does not take into account expenses for travel, accommodation, and recovery. Patients may be aware of the costs and some of the risks, said Hache, but cases like this show how many unknowns remain regarding the long-term effects of unproven stem cell therapies.
“The patient probably figured, at the end of the day I guess I lost that money and I am not any better,” Hache said. “Not realizing that there was a worse outcome.”