Stem Cells Reduce Pain from Knee Osteoarthritis

By Pat Anson, PNN Editor

A small new study has demonstrated that stem cells collected from a patient’s own bone marrow can significantly reduce pain caused by osteoarthritis of the knee.

In the first clinical trial of its kind in Canada, researchers collected mesenchymal stromal cells (MSCs) from the spines of 12 middle-aged patients with moderate to severe knee osteoarthritis. These “autologous” cells – stem cells derived from a patient’s own fat or bone tissue – were then processed and injected back into the patients’ knees at different doses.

Researchers then followed the patients for the next 12 months, using MRI imaging, biomarkers, molecular fingerprinting and the patient's own assessment of how they felt.

"Our goal was to test for safety as well as to gain a better understanding of MSC dosing, mechanisms of action and donor selection," said lead author Sowmya Viswanathan, PhD, Arthritis Program at the Krembil Research Institute, University Health Network in Toronto.

At the end of the study period, researchers said there were significant improvements in all 12 patients’ pain levels, stiffness and quality of life. The study also showed that the MSCs were safe at all the doses tested and that the higher the dose, the more effective the outcome.

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"We also obtained novel insights into a potential anti-inflammatory mechanism of action of these cells in osteoarthritic knee joints. We noted that donor heterogeneity is an important factor, and our assembled panel of genes helps us identify cells which are potent in osteoarthritis. These are important findings which we hope to translate into a larger, powered clinical trial as part of our next steps," said Viswanathan, who reported the findings in the journal Stem Cells Translational Medicine.

Over 250 million people worldwide suffer from knee osteoarthritis (OA), which causes thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA.

Knee replacement and arthroscopic knee surgeries are commonly used to treat knee OA, even though many studies show they have limited effectiveness. A 2017 study in The British Medical Journal  of over 7,400 patients who had knee replacement surgery found the procedure often had minimal effects on quality of life and wasn’t worth the cost.

Arthroscopic surgery is less invasive than a total knee replacement, but studies also show it is often not effective. In 2017, an international panel of experts reviewed 25 studies involving nearly two million patients and concluded that arthroscopic surgery does not improve long term pain or function in patients with knee conditions such as osteoarthritis.

Because these conventional treatments often fail, there is growing interest in the use of stem cells to treat knee problems. The FDA, however, takes a dim view of autologous stem cells and released guidance in 2017 that requires the cells to undergo “minimal manipulation.”

The FDA recently sent letters to 20 stem cell manufacturers and clinics warning them they were violating FDA regulations. The agency says the science behind autologous cells is still in its early stages and they have not been proven to be safe and effective.

“There’s a false premise being asserted by some in the field that a product derived from a person’s own body and then manipulated and reinserted for another use different from the one it played in its original location is not subject to FDA regulation just because it originated from the person it was given back to,” then FDA commissioner Scott Gottlieb, MD, and Biologics Center Director Peter Marks, MD, said in a statement.

“We’ve seen too many cases of sponsors claiming that cells aren’t subject to FDA regulation just because the cells originated from the same patient to whom the eventual manufactured product is being given. And we’ve seen too many cases of companies making unsubstantiated claims that these treatments prevent, treat, cure or mitigate disease where the products have sometimes led to serious patient harm.”

FDA Seeks Shutdown of Stem Cell Clinics

By Pat Anson Editor

The U.S. Food and Drug Administration has stepped up its crackdown on the stem cell industry by filing two complaints in federal court seeking permanent injunctions against stem cell clinics in Florida and California.

US Stem Cell of Sunrise, Florida and California Stem Cell Treatment Center are accused of marketing stem cell products without FDA approval and for “significant deviations” from safety and manufacturing guidelines. Both companies said they would “vigorously defend” themselves and challenge the FDA’s authority to regulate autologous stem cells, which are made from a patient’s own blood or tissue.

The  lawsuits could ultimately decide the fate of hundreds of stem cell clinics that have opened around the country in recent years, offering new therapies for arthritis, neuropathy, degenerative disc disease and other chronic conditions.

“Cell-based regenerative medicine holds significant medical opportunity, but we’ve also seen some bad actors leverage the scientific promise of this field to peddle unapproved treatments that put patients’ health at risk. In some instances, patients have suffered serious and permanent harm after receiving these unapproved products,” FDA Commissioner Scott Gottlieb, MD, said in a statement.

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In 2015, three elderly women became legally blind after having unapproved stem cell treatments for macular degeneration at US Stem Cell. The clinic was also warned by the FDA last year to stop using adipose tissue (body fat) to make stem cells that were injected into the spinal cords of patients.

The FDA alleges that California Stem Cell Treatment Center – which has clinics in Beverly Hills and Rancho Mirage -- is also using stem cells derived from adipose tissue to treat patients suffering from arthritis, stroke, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), diabetes, cancer and other conditions.

“The unproven and potentially dangerous treatment was being injected intravenously and directly into patients’ tumors,” the FDA said.

The case against California Stem Cell could have a broad impact because it also targets the Cell Surgical Network Corporation (CSN), which has a chain of about 100 stem cell clinics. At issue in both lawsuits is whether a patient’s own stem cells can be used for therapeutic purposes and are outside the control of federal agencies like the FDA.

“CSN strongly rejects the idea that a person’s own cells should be regulated by FDA as a drug,” Dr. Elliot Lander of CSN and California Stem Cell Treatment Center said in an email to The Niche, a stem cell blog.

“We share FDA’s concern for patient safety, but do not believe that FDA regulation of a surgical procedure that simply harnesses the healing power of a patient’s own cells, without altering the biological characteristics of those cells, is the answer. The decision of whether or not the surgical procedure is performed should be made by the patient and physician – not the FDA or any other arm of the federal government.”

US Stem Cell also released a statement on its website, saying it would “vigorously defend medical freedom of Americans.”

FDA Moves Forward on Stem Cells

By A. Rahman Ford, Columnist

The Food and Drug Administration is finally getting the message.

In a special report published in The New England Journal of Medicine, the FDA makes a clear and positive shift in its stem cell policy – conceding that the old paradigm of drug approval just doesn’t work for stem cells.

The report, entitled “Balancing Safety and Innovation for Cell-Based Regenerative Medicine” is authored by FDA Commissioner Scott Gottlieb, MD, and Peter Marks, MD, Director of the FDA’s Center for Biologics Evaluation and Research. 

Although short on specifics, Gottlieb and Marks declare their openness to creating alternative paths toward FDA approval of stem cell products – a policy change that could help stem cell therapies get to market faster and help patients sooner. This is a welcome move by the FDA. 

The tone used by the authors signals that the FDA is listening to the voice of the people and stem cell developers. Gottlieb and Marks wrote the FDA must take “an original policy approach to the regulation of a highly innovative field, one in which [the FDA’s] traditional approach to regulation may not be as efficient or effective as in more mature fields.” 

They maintain further that by working “within the existing regulatory framework” and by adopting “new principles,” the FDA’s premarket evaluation of stem-cell therapies will become more efficient. 

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It seems the agency could no longer ignore the fact that patients – such as those who suffer from chronic pain – cannot wait for the rusty gears of the antiquated clinical trial process to churn out the treatments they need to save their lives.

FDA Breaks with Past

The tone set by Marks and Gottlieb differs significantly from that of Gottlieb’s predecessor, Robert Caliiff, MD, who co-authored a NEJM article last year entitled “Clarifying Stem Cell Therapy’s Benefits and Risks.”  As I’ve previously discussed, the arguments made by Califf were seriously problematic, specifically with regard to autologous therapies, which use stem cells made from a patient’s own blood or body tissue  

Although Califf and his co-authors acknowledged the “unique challenges of stem cell clinical research,” their overall posture was decisively rigid in regard to new approaches to FDA approval.  As an indication of just how low of a priority outreach was to them, they made no mention of working with stem cell investigators and sponsors until the final sentence of the article.  For the previous regime, outreach was an afterthought.

Marks and Gottlieb seem to be taking a more conciliatory approach by extending a regulatory olive branch to stem cell physicians and small clinics.  Unlike previous FDA statements, they spent less time on the spurious issue of safety and instead pivot toward the effectiveness of treatment and moving forward with commercialization.  In doing so, the they acknowledge that the novelty of stem cell technologies require a more flexible path toward approval.

To accommodate this move and to facilitate the expedited availability of stem cells to patients, the FDA will use the expanded authorities granted it by the 21st Century Cures Act.  The Cures Act allows the FDA to use non-traditional types of data – such as clinical data – to receive FDA approval.  Notably, the FDA will be incorporating some “new concepts for how small investigators and firms can seek and meet the approval standard for products through efficient expedited pathways.”  This is a step in the right direction.

How exactly will this work in practice?  No one really knows.  Marks and Gottlieb only provide one theoretical example: the FDA will provide “tools” to allow small firms to work collaboratively to obtain a biologics license for physicians, researchers and clinics.

Any outreach by the FDA should be welcomed and any attempt to expedite the availability of stem cell therapies to patients who need them should be encouraged.  However, given the dearth of detail offered by Gottlieb and Marks, precisely how these alternatives will work in practice remains nebulous.  Thus, the overtures made by the FDA are – at this point -- best met with skepticism and a cautious optimism

If the FDA is truly open to novel approaches to stem cell regulation, it should devise separate rules for autologous therapies – which former Commissioner Califf acknowledged “raise fewer safety concerns than allogenic cells.”  Regulation of autologous therapies by the FDA should be minimal, with the majority of oversight left to state governments and their agencies.

These new policy changes by the FDA are forward-thinking and should proceed further.  However, as promising as those options appear, they should in no way be construed as delegitimizing or nullifying legislative advances made in Texas or those that will be made when Congress enacts “Right to Try” legislation. 

All of these options can function cooperatively to ensure that the patients – often the most overlooked quantity in the medical policy equation – can receive the life-saving and curative treatments they need as soon as possible.

The FDA may offer many paths, but it need not be the only path.

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A. Rahman Ford, PhD, is a lawyer and research professional. He is a graduate of Rutgers University and the Howard University School of Law, where he served as Editor-in-Chief of the Howard Law Journal. He earned his PhD at the University of Pennsylvania.

Rahman lives with chronic inflammation in his digestive tract and is unable to eat solid food. He has received stem cell treatment in China.  

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.