Stem cell therapies often not the wonder treatment they may seem

While stem cells offer almost unlimited promise, private clinics are exploiting vulnerable patients by selling them untested, dangerous procedures.

Stem cells have lifesaving potential in a narrow set of diseases.

“Stem cell miracle” headlines are easy to find: the self-renewing, cell-replenishing machines hiding in our tissues are touted as fixing any condition you can name: ­arthritis, multiple sclerosis, cancer, ageing, blindness, even autism.

But while stem cells have lifesaving potential in a narrow set of diseases, and researchers are busy testing them for a huge number more, many therapies on offer have yet to pass the rigorous process of trials to ensure their safety and efficacy.

Around the world, and increasingly in Australia, private clinics have sprung up to offer unproven treatments to patients who haven’t time to wait or who can’t get into a trial. Researchers, doctors and ethicists say this not only fleeces patients and exposes them to unacceptable risk of infections, tumours, bleeding, strokes and other adverse events, even death, it also obstructs legitimate clinical research and erodes trust in the field.

“Scientists have discovered all these great attributes of stem cells and want to harness them, and the public’s quite enthused — but we’re nowhere near delivering on the promise,” says Megan Munsie, head of engagement, ethics and policy at Stem Cells Australia and deputy director of Melbourne University’s Centre for Stem Cell Systems.

“There’s this expectations gap between what we’re doing in the lab and what the community might want us to do or think we can do already. And into that gap have stepped all these commercial clinics.

“We started off with a handful of clinics in far-flung nations around the world, in areas where there was no or ­limited jurisdiction. But recently we’ve seen a lot of doctors, particularly those with access to liposuction ­machines, opening clinics in Australia and America because they can use the patients’ own cells at their discretion. They market it as stem cells, they believe they’re putting stem cells back in the ­patient, but it’s often very disconnected from the science of stem cell biology.”

There are two main modes of stem cell therapy. Haematopoietic stem cell transplantation, which uses stem cells to reconstitute bone marrow after high-dose chemotherapy, is well established for cancer and is being investi­gated for other immunological ­diseases.

Ian Kerridge is a haematologist and bone marrow transplant ­physician at Royal North Shore Hospital in Sydney, chairman of the Australian Bone Marrow Donor Registry and a professor of bio­ethics and medicine at the University of Sydney.

“The stuff that’s clear and straightforward is using auto­logous (your own) and allogeneic (donor) cells for bone marrow transplant,” Kerridge says. “Rheumatoid arthritis, scleroderma, multiple sclerosis — they’re all on the edges of investigation, becoming more or less proven as the data accumulates. So there are clinical trials, but not everyone gets in. People don’t want to wait so they find someone who’ll offer them the same treatment outside the context of a clinical trial. Some people are just saying, ‘Fine, I’m paying my $100,000 and going to Moscow or Mexico City. ”

Another kind of treatment, so-called mesenchymal stem cell therapy, takes cells from fat or connective tissue to treat a wide range of conditions, most commonly osteoarthritis. It is this kind of intervention that is offered by private clinics, with cells harvested through liposuction and reinfused intravenously.

But while stem cells can be identified and counted, and can be relied on to find their way back to where they came from, in haematopoietic transplantation, there is no reason to expect fat cells ­injected into the bloodstream will magically home in on a sore joint or the brain and fix arthritis or ­dementia. There is also little information about how private clinics process the cells they ­extract.

“When these people extract the fat, we don’t know what they do with that material and what they put back in,” Sydney University associate professor of bioethics Wendy Lipworth says. “We have no idea what this sort of ­‘Nutribullet’ preparation ends up containing. It’s one thing to put it into a joint, but for a lot of these other conditions they put it into the bloodstream, hoping the cells will somehow find their way to the right part of the body and do this magic once they get there.”

Gerhard Bauer and his team counted the reports in scientific literature and the media of bad outcomes from unproven stem cell interventions before publishing a long and stomach-turning list this year in Stem Cells Translational Medicine.

A 13-year-old boy from Israel with a neurodegenerative disease went to Russia to have neural cells injected into his brain and cerebrospinal fluid, and grew a tumour from the donor cells. American Jim Gass travelled to Mexico, China and Argentina for stem cell treatments after a stroke and developed an enormous mass on his spine, causing paraplegia, again from the donor’s cells. Three women with macular degeneration had their own fat cells ­injected into their eyes at a US clinic (Bioheart, now trading as US Stemcell) and lost their sight.

In Australia, Sheila Drysdale, 75, of Sydney, who had dementia, died after liposuction in 2013. A coroner found her doctor, Ralph Bright of Macquarie Stem Cells, had not ensured that she had stopped taking her blood thinners, and when she suffered blood loss leading to hypovolemic shock — a known risk of liposuction — failed to send her straight to hospital.

The most egregious aspect of her death, Kerridge says, is that ­injecting adipose cells intra­venously to treat dementia is an intervention for which there is “not even a shred of evidence”.

At the inquest in 2016, deputy state coroner Hugh Dillon recommended an investigation, saying: “The reasonableness or appropriateness of applying this experimental procedure to Sheila Drysdale is highly questionable … Dr Bright appears to have no idea whether the procedure has any genuine therapeutic value.”

The regulation of stem cell treatments is shared by the Therapeutic Goods Administration and the Australian Health Practitioner Regulation Agency. The TGA ­regulates products, including “biologicals”, with an exemption for tissues taken from a patient to be used on the same patient, by a registered medical practitioner, or in a hospital for a patient in that hospital.

Since July, private clinics have been banned from advertising services direct to consumers, and ­clinics are on notice that from July next year the kind of procedure Bright performed on Drysdale will be subject in some cases to TGA regulation. The AHPRA oversees practice, in co-regulation with the Medical Council of NSW in that state and with the health ombudsman in Queensland. This oversight, Lipworth says, does not prevent doctors from “innovating” with unproven interventions.

The Medical Council of NSW imposed some restrictions on Bright’s licence in 2016 but he is still allowed to treat patients from whom he has already harvested cells and to take on new patients for osteoarthritis treatment.

“It’s quite problematic,” says Lipworth, “because it left the ­impression that there was this clear distinction between osteo­arthritis and the other types of ­intervention — it was in a way validating osteoarthritis interventions.” This is despite a statement from the Australasian College of Sport and Exercise Physicians that there was insufficient scientific support for this treatment.

The council tells The Australian it “considered it appropriate to ­impose restrictions on Dr Ralph Bright in the public interest and to protect the health and safety of the public. Proceedings under s150 (of the Health Practitioner Regulation National Law [NSW]) are not public, nor may the reasons for decision be published.”

Because of the lack of high-quality evidence, the council considers stem cell treatments for osteoarthritis “a ‘complementary’ therapy”, meaning not scientifically validated.

Kerridge says dissatisfied ­patients theoretically have several avenues of recourse: AHPRA, the TGA, the Health Care Complaints Commission and consumer legislation. But complaints are rare.

“Patients are very vulnerable. They’d have to say, ‘I was an idiot, I was coerced into this, I was crowdfunded $100,000 by my friends and family, and this has been of no benefit at all — and I’m happy for all that to be on the public record.’ People aren’t going to do that.”

Lipworth adds: “And what happened with Ralph Bright was an exception — most patients are not hurt, they’re just spending $80,000 on something that doesn’t work.”

Munsie says it is often hard for patients to complain after a failed treatment that may have ­diverted them from a more standard therapy.

“I’ve met people who feel outraged about it but are now too ill to make a complaint — they can’t ­invest in it, they want to move on. In one example I asked them to speak out to the media but they didn’t want to — they felt they had to divert their energies into care rather than complaint.

“When the TGA was undertaking a review (into stem cell therapy), there were a lot of questions as to why there weren’t more complaints to the HCCC, to AHPRA, and I was trying to point out that those processes aren’t simple and the people who’ve been through this feel like it’s a failure of theirs that the treatment hasn’t worked.”

Another stem cell “service” that elicits outrage is private cord blood storage, marketed using emotive imagery to mothers-to-be. Cord blood is an easily accessible source of donor stem cells for haematopoietic transplants; AusCord is the Australian public bank for storing cord blood stem cells.

But undermining this public ­resource, Kerridge says, are the businesses convincing mothers to store their own baby’s cord blood for thousands of dollars a year. It’s a terrible investment, and not only because the likelihood of acquiring a disease treatable with stem cells is somewhere between one in 25,000 and one in 250,000.

“If you develop something nasty, often you don’t need your stem cells, you need someone else’s. If you need autologous stem cells, we just get them from you at that time,” he says.

“And by the way, that’s all covered by Medicare. You don’t need to pay for 50 years of storage for something that will come out with a storage injury as well. It’s a total scam.”

Lipworth says further or ­tougher regulation is not the ­answer. “I’d like to see the current processes we have used in more ­effective ways,” she says. “We don’t want to stifle innovation but we need to have systems in place to, if not prevent, then at least stop people in their tracks when they take advantage of people.”

Kerridge would like to see “a genuine conversation about the co-opting of science and research and medicine for nefarious ­commercial ends. We need a genuine discussion about medicine at the margins.”

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STEMMING THE TIDE

-Avoid treatments that don’t have a Medicare number and are not recognised by your insurer

-You should not have to pay to participate in a clinical study

-A cosmetic surgeon offering treatments for dementia, autism or osteoarthritis is a red flag

-Beware a clinic offering the same kind of intervention for multiple conditions

-Seek a second opinion from someone who is not selling you the product

-Patient support groups for your condition, e.g. MND Australia and MS Australia, can help you navigate and connect you

Embryonic stem cells can develop into any cell type.

WHAT ARE STEM CELLS?

-Stem cells are undifferentiated cells that have the capacity to self-renew and, given the appropriate cues, to differentiate into more than one cell type.

-Embryonic stem cells are derived from the inner cell mass of blastocyst-stage embryos; they can self-renew indefinitely in culture and can develop into any cell type

-Adult (or somatic) stem cells can be derived from most organs and typically differentiate into cells types specific to that organ

-Differentiated adult cells can be reprogrammed into ‘induced pluripotent stem’ cells, with self-renewal capacity and pluripotentiality similar to ES cells