Stemming The Flagrant Cells

Those who are shouting that stem cell therapy is the next big thing are on shaky ground reckons researchers in the field. By Basia Chow

The past decade has seen the emergence of clinics offering unproven, dangerous stem cell therapies which have gradually become more prevalent and easily accessible. One may be sitting right on your doorstep — or your web browser.

According to the International Society on Stem Cell Research (ISSCR), only three stem cell therapies are currently approved for therapeutic use — bone marrow transplants, skin grafts and cornea injuries. All other stem cell therapies are still in the experimental phase and carry risks, and should not be made available to the public.

“Clinics claiming their stem cell therapies can cure cancer and so on do not subscribe to ISSCR guidelines and aren’t part of mainstream treatment,” asserts Associate Professor Dan Yock Young, Head of the Department of Medicine in the National University of Singapore (NUS).

“The cells you intend to use may have an unintended effect,” explains Dan, who has conducted research on liver stem cells since 2003. “If you insert stem cells into an injured spinal cord, they can form scar tissue across the spine’s nerves, which will worsen the patient’s condition.”

In addition, as stem cells are highly proliferative, they can potentially cause cancer. Furthermore, the effect of stem cells on other parts of the body are not confirmed and can have harmful repercussions. For instance, liver stem cells may move to a patient’s lungs and clog up their vessels.

The X-Cell centre in Germany came under increasing criticism in 2010 when an 18-month-old baby who had stem cells injected into the brain died. More recently, celebrated scientist Paolo Macchiarini from Karolinska Institutet in Sweden was fired for scientific negligence in March 2016, after causing six deaths when he had artificial tracheas coated in stem cells transplanted into patients.

Taking Root
However, not all experimental stem cell therapies are fraudulent or high-risk. In fact, clinical trials offering experimental therapies are an essential for scientific development.

But what has been a cause for concern are the proliferation of clinics offering experimental stem cell therapies which have not been proven to be safe or effective for clinical trial, observes Assistant Professor Tamra Maree Lysaght from the Centre for Biomedical Ethics at NUS.

These entrepreneurial medical practitioners advertise their services via the Internet, charging their patients exorbitant fees. “Some of these clinics genuinely believe they’re trying to do something for the patient, even if it’s not going to work,” acknowledges Tamra.

What is worrying is that these clinics have emerged even in high-income, developed countries with extensive investments in high-level biomedical research and healthcare. “In the US, they number in the hundreds at the moment,” says Tamra. “The numbers are so great now that they’re out of the US Food And Drug Administration’s (FDA) control. And to top it off, they’re nebulous. If they’re issued an order to shut down, they move elsewhere, get a new license and set up their practice again.”

In Australia, there are more than 40 clinics operating, though laws explicitly exclude certain stem cell treatments. And Tamra’s preliminary analysis of major areas like Tokyo and Osaka in Japan has identified 20 clinics.

The Internet has made it easy to promote anything, including unproven cell therapies offered by clinics. The Cell Surgical Network in the US, for instance, has created a powerful online presence and has made its services available in multiple clinics across state lines.

Yet, its site asserts that the franchise “does not claim that any applications…using autologous stem cells are approved by the FDA, or are even effective.”

The market for stem cell therapy looks like it is set for more growth at 25% per annum beginning 2012 and ultimately reaching the US$120 billion mark in 2018, according to a Transparency Market Research report, the Stem Cells Market Global Industry Analysis. The rise of medical tourism and unmet medical needs are the main drivers for this growth, and there will continue be an increase in demand for regenerative treatment (stem cell therapy) options.

Don’t Believe Everything You Read
This surge in demand is often fuelled by inaccurate and incomplete media portrayal of the industry.

In a 2010-2013 study, Stem Cell Hype: Media Portrayal Of Therapy Translation, it was revealed that out of 307 publications in major newspapers, 57.7% report an optimistic outlook on the future of stem cell research. Unrealistically, 69.7% of these publications claim that stem cell therapies will be available within a decade or ‘just around the corner’.

“Stem cells have been over-hyped,” Tamra agrees. “The embryonic debates may have influenced the public consciousness into believing stem cell therapy would provide miracle cures for everything. But that has turned around on the field itself because it has attained a mythological status.”

Riding on this, patients are demanding their right to “miraculous” stem cell therapies.

In 2006, treatments claiming to be effective against neurodegenerative disorders were marketed by the Stamina Foundation without regulatory approval or proof. Although the treatment was banned by health authorities in 2012, the ruling was overturned in 2013 and the case re-opened due to significant public outcry.

“Despite concerns about the lack of scientific justification, and allegations of criminal conduct involving fraud…patients continued to seek the treatment up to 2015,” says EuroStemCell.

“The Western biomedical perspective is conservative, so it takes quite some time for new therapies to develop,” confirms Dan. “New therapies are potentially dangerous; bone marrow transplants took almost 30 years to evolve.”

Laws And Regulation
This raises the question: what constitutes a reasonably safe and effective stem cell clinical trial? According to Dan, such a therapy necessitates several elements. “You need controls and a certain significance before making a conclusion. It has to be validated in alternative models of injury to make sure it’s a consistent observation and not artificial. Ultimately, you have to publish it on the international literature scene so other groups will replicate it and make sure it is reproducible before you accept it as fact.”

But picking out which stem cell therapies are reliable becomes more difficult as clinics register for clinical trials and publish in open access journals, giving dangerous operations a veneer of scientific credibility and legitimacy. “(And) unless you know the scientific methodology behind clinical trials, translational medicine and scientific research, it’s very difficult to distinguish that this is a whole bunch of rubbish,” Tamra bluntly says.

“There’s no set scientific standard (for what constitutes a reliable therapy),” she continues. “It varies depending on the complexity of the biotech that you’re using, how targeted it is and how it interacts within the body. And humans aren’t all built the same. Trying to develop a basic level of evidence to be established before clinical trials are introduced is an active project of ours at the moment.”

There is currently no international legislation governing stem cell therapy. Instead, what is keeping the unproven stem cell therapies in check is local regulation. “That is, if you’re lucky enough to live in a well-regulated country,” says Dan. “It’s a double-edged sword. You’re hampered from seeking new novel therapies but the rules protect you.”

For instance, despite not having any laws exclusively prohibiting stem cell therapy, Tamra says that between 2007 and 2010, the Singapore Medical Council (SMC) took action against three practitioners offering stem cell therapies outside of clinical trials, charging them with professional misconduct and imposing fines and censures.

The Singaporean doctors were not removed from the medical register, and one doctor had the ruling overturned on the basis that there was no established standard for the practice of aesthetic medicine at the time of treatment.

In Austria, the derivation of embryonic stem cell lines is banned, but the use of imported embryonic stem cell lines is permissible. And Ireland takes a more liberal approach, with no laws specifically banning the research and use of stem cells.

This lack of standardised regulation means that ultimately, there isn’t anything stopping a patient slipping through the cracks or flying somewhere with lax rules on stem cell therapies.

Knowledge Is Power
In light of this, it doesn’t hurt to know what to look out for in a safe and effective stem cell therapy. For instance, a well-designed trial usually takes a narrow patient population since not everyone is eligible for a specific treatment, but fraudulent clinics will still sell ineffective or dangerous treatments to you anyway. Other red flags include a reliance on patient testimonials as evidence, a lack of information documenting the treatment protocol, and claims that there are no risks, along with high treatment charges, according the ISSCR’s Patient Handbook on Stem Cell Therapies.

If you find a stem cell clinical trial which doesn’t raise any alarms, you can ensure your human rights and safety by ascertaining that certain steps are taken. A legal document known as an Informed Consent Form can be drawn up, asserting that the medical providers are liable for misconduct and scientific negligence. It’s also good to double-check that preclinical studies of the treatment are published and peer-reviewed, and that the treatment has received approval from independent committees and national or regional regulatory agencies.

Bright Side
Around this gloomy cloud, there is a silver lining. Just this year, several notable advancements were made in the field of stem cell research. Harvard and MIT researchers successfully inserted insulin-producing cells into mice, which may mean that type 1 diabetes patients may only need insulin shots once every several years in the future. In another case, a rapid improvement in stroke patients’ symptoms was observed when Stanford researchers injected stem cells into locations of the brain damaged by stroke.

“Commercial and private investments in stem cell therapies will play contingent roles (in research and development),” says Tamra. Research agreements between academic and commercial entities, for example, ensure that stem cell studies remain rigorous and transparent, while providing scientists with necessary financial aid and technical resources. “(But) they should be concerned about how well they understand the science. Unless you’re talking to an academic or scientist who is genuine in establishing the safety and effectiveness of a stem cell therapy, I think it’s a very high-risk investment.”

Ultimately, the key takeaway should be that stem cell therapies are not magic and can be dangerous in the wrong hands. “It is a tool,” says Dan. “It’s far too simplistic to say that stem cells are a cure-all for diseases.”

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