Stem cell treatment for damaged knees
Years of playing Australian Rules football left Wafa Zaza with a knee so badly damaged he was in regular pain and finding it hard to live a normal life. He was only 30.
After an initial cartilage tear at the side of his right knee, Zaza had surgery to allow him to get back to the sport and exercise he loved. But six months after recovery a second and more serious tear in the same knee placed him in a predicament.
“It was no longer a case of trying to get back to sport – it was now affecting my day-to-day activities, from driving, carrying groceries and even sitting in a cinema,” he says. He also had another problem: “I was too young to get a knee replacement.”
In 2017, the then 33-year-old joined a pilot case series run by the Melbourne Stem Cell Centre for people under 60 who had severe knee damage from sport and other trauma. Its aim was to repair and regrow lost cartilage through mesenchymal stem cell treatment combined with arthroscopy surgery.
Zaza’s recovery has been reflected in the evaluation paper published in the international peer-reviewed journal Regenerative Medicine in July this year, in which all participants – the average age of whom is 36 – experienced progressive additional improvement in pain and mobility. Their average pain improvement was 60 per cent. Cartilage regrowth among the group was supported by MRI tracking. Participants reported no severe side effects.
Embryonic stem cells, which begin developing days after conception, are blank slates that are able to grow and differentiate into specific cells throughout the body. Mesenchymal stem cells are multipotent stem cells that are important for making and repairing skeletal tissue. They are less potent than the embryonic cells that were first used in stem cell research, but they can be isolated from certain tissue in adults such as bone marrow and fat.
As a sports physician, head researcher Associate Professor Julien Freitag sees many acute musculoskeletal injuries “and unfortunately they often lead to long-term degenerative conditions like osteoarthritis [OA], which is an increasing morbidity among the young and older populations”.
His ultimate aim with the younger cohort is to now follow up with participants every two years to assess the treatment’s effectiveness as an intervention to either prevent or delay the late onset of OA, which affects one in six Australians.
What separates Freitag’s research from similar studies in leading research facilities internationally is that he has chosen to use adipose tissue, or fat, for stem cell harvesting rather than bone marrow.
“Comparatively, adipose tissue has a richer source of mesenchymal stem cells, which are useful for musculoskeletal complaints. So they’re easy to harvest, and it is a relatively safe and minimally invasive procedure under local anaesthetic,” he says.
“The unfortunate thing with existing interventions for degenerative conditions in the knee is they are more aimed at symptom control rather than modifying the progress of the condition and the eventual need for joint-replacement surgery.”
International stem cell research has been conducted for decades and its progress has had its highs – with Nobel prizes for groundbreaking research – as well as deep lows. In 2014 a renowned researcher at Harvard Medical School, Dr Piero Anversa, was alleged to have used falsified and/or fabricated data in more than 30 studies suggesting stem cells could replace cells lost through heart attacks and heart failure.
Over the years, the early hope that stem cells would be biological miracle workers took on a more realistic flavour with the understanding that many more questions needed to be answered to bring stem cells more broadly into mainstream medicine.
To that end, the federal government through its National Health and Medical Research Council has contributed nearly $724 million since 2010 towards stem cell research in several fields of medicine. A separate government body, the Medical Research Future Fund, which was established five years ago, has also provided more than $53 million for stem cell-related research. This includes $2 million for research projects using stem cell-derived tissue models to rapidly test drugs already approved for use in humans for protection against Covid-19.
Peak bodies such as the Australian Orthopaedic Association (AOA), Arthritis Australia and the Royal Australian College of General Practitioners, however, maintain that evidence is still insufficient to recommend stem cell treatment for arthritic or injured knees.
AOA president Dr Andrew Ellis, in a written response on stem cell therapy, said: “Stem cell treatments for knee osteoarthritis have no current role in the everyday management of knee osteoarthritis. At this time, they remain an interesting treatment but one that is costly and unproven. The benefits [from research] have not materialised yet in a way that allows use or recommendation for treatment.”
Arthritis Australia’s acting chief executive, Franca Marine, says while stem cell treatment showed “great promise” research was not yet conclusive.
“Clinically unproven stem cell therapies may pose serious health risks. These include infection, ectopic tissue formation [growth of body tissues in the wrong place] and allergies,” she adds.
Dr Freitag’s various studies in the past six years have largely attracted positive media attention, with the notable exception of an ABC Media Watch segment criticising what it called “hype” contained in a media release on the results of an osteoarthritis treatment pilot study among an older cohort of patients.
While he was disappointed with what he deems “unbalanced and ill-informed” commentary, Freitag says he understands conventional medicine’s cautious approach, and agrees ongoing rigorous and ethical research is crucial.
While the slower-than-expected pace of stem cell discovery frustrates many, the University of Melbourne’s Professor Megan Munsie, who is director of Stem Cells Australia, which was formed in 2011 to encourage research and education in this field, believes all research must be tempered with patience to allow for thorough investigation at every step of the process before it becomes mainstream.
“We need to keep incentivising clinical research, and while there is growing evidence to suggest a role for cell-based interventions in some orthopaedic procedures, there remains many questions still to resolve,” she says. “These include justification for the approach, what type of cell is required, how should we put them back in and what type of patient would benefit.”
Munsie says her main concern is the proliferation of unscrupulous clinics that use websites and social media platforms to spruik expensive stem cell solutions for procedures ranging from arthritis to dementia to multiple sclerosis.
She has 70 websites on her watchlist and more keep popping up even though the regulatory body, the Therapeutic Goods Administration, last year tightened the rules regarding advertising by these clinics.
“The ones I’m particularly worried about are the fly-in fly-out clinics, which set up as some sort of speciality hub even though the interventions are yet to be proven, and you may never get to see that doctor again,” says Munsie.
“Ultimately, the patients are the ones who have to make up their own minds, but I do believe an independent second opinion from someone who is not directly profiting from the sale of these unproven interventions is crucial.”
Wafa Zaza says prior to the stem cell implant he had tried four conventional knee treatments, including microfracture, before turning to stem cells.
“I did some research and my wife, Sarah, was fully behind my decision because she was worried what raising a family would look like with me not being able to carry out normal activities around the house,” he says.
“The extraction of the stem cells using liposuction just under the skin on my stomach felt a bit odd but I wouldn’t say it hurt. It took about two months to spin up the cells and then the abrasion arthroplasty to prepare the site was booked in a day before the cells were deposited back.”
Zaza received 50 million stem cells at baseline and the same amount six months later, with a quantity of the cells isolated for use if required later.
“I had to wear a special brace everywhere for the first month to give the knee stability, and I’d say it took nearly a year before I started to return to normal activities like short runs or a little basketball,” he says. “I no longer have pain driving, sitting or sleeping, and some days I sometimes forget I ever had a knee issue.
“On the odd occasion, if I’ve done a heavy day of sustained weight-bearing activity, the knee will start to ache and I think I’ve stuffed it again, but within a few days it disappears, whereas it used to take weeks to clear.”
It cost Zaza about $13,000 for the double procedure, which included an overnight stay at Glenferrie Private Hospital in Melbourne’s east for the arthroscopy.
“I considered the risk I was taking, but at that point of my life I had resigned myself to just living with the pain, so for me the main risk was that it wouldn’t work,” he says.
Zaza and his wife now have two daughters, aged five and two.
“I play with the kids and pick them up with no trouble,” the proud father says. “Just recently I built them a cubby in the backyard and there is no way I could have done that before I got the stem cells.”
This article was first published in the print edition of The Saturday Paper on Oct 10, 2020 as "Growth industry".
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