FDA Approves Stem Cell Study for Degenerative Disc Disease

By Pat Anson

The Food and Drug Administration has given the go-ahead for a late-stage clinical trial of an injectable stem cell product that could give new hope to millions of patients suffering from lower back pain caused by degenerative disc disease (DDD).  Up to 400 patients with mild to moderate DDD are expected to enroll in the Phase 3 study later this year.

The trial is being conducted by DiscGenics, a Utah-based biopharmaceutical company that is developing new cell-based therapies for musculoskeletal conditions. It’s one of the first late-stage studies of a stem cell product to win approval from the FDA, which has been openly skeptical of cell-based therapies due to lack of evidence proving their safety and efficacy in clinical trials.

The only stem cell therapies currently approved by the FDA are used to treat sickle cell disease and some cancers. Approval of a stem cell product to treat degenerative discs would be a big step forward for regenerative medicine, and give patients an alternative to fusions and other more invasive spinal procedures.

“The FDA has been very familiar with our process, our product, and the chemistry, manufacturing and controls for quite some time,” says Flagg Flanagan, CEO and Chairman of DiscGenics. “We feel really good about where we are in terms of the patient reported outcomes. But most importantly about the safety. We feel like this cell is extremely safe to be used on human patients and we're feeling really, really good that we can help a lot of people.”

Discgenics’ injectable disc cell therapy (IDCT) is a single-injection biologic treatment designed to halt the progression of lumbar DDD by regenerating the disc “from the inside out.” The active ingredients in IDCT are enriched stem cells known as discogenic cells, which are derived from donated adult human disc tissue.

IDCT has been granted regenerative medicine advanced therapy and Fast Track designations by the FDA. Approval of the Phase 3 study came just weeks after Discgenics released positive results from a combined Phase 1/Phase 2 human trial of IDCT, published in the International Journal of Spine Surgery.

In that study, 60 patients with mild to moderate DDD were randomly assigned to receive an injection of either low-dose discogenic cells, high-dose cells, or a placebo. After one year, patients in the high-dose group had an average reduction in pain intensity of nearly 63 percent, along with significant improvements in their disability and quality of life. The regeneration of discs, which was monitored through MRIs and other imaging tests, was sustained two years after the injection.

“Things even came out a little better than we even expected,” Flanagan told PNN. “We showed very good durability, out to two years with the high dose patients. Anecdotally, we continue to follow some of those high dose patients and we have data in a pretty good cohort out to three years. We have a couple (patients) out to four years and the durability still seems to hold pretty well.”

The Phase 3 trial will consist of two parallel studies of IDCT that will also be randomized and placebo-controlled. Like the two earlier trials, each study will last for two years to assess the long-term safety and efficacy of IDCT. The first participants are expected to be enrolled in the final quarter of 2024.

“We'll start looking for patients and reviewing patient profiles that want to apply for the study shortly,” Flanagan said. “I think this is something where we can help many, many patients hopefully avoid a surgical intervention with an injection in a treatment room.”

People interested in getting updates on the Phase 3 IDCT trial or volunteering for it can submit their contact information to DiscGenics here.

Mesoblast, an Australian company specializing in regenerative medicine, recently began enrolling U.S. patients with chronic low back pain in a Phase 3 study of its proprietary mesenchymal stem cells, which are derived from young and healthy adult donors.

Stem Cells Can Restore Movement in Paralyzed Patients

By Pat Anson, PNN Editor

Stem cells derived from body fat can improve sensation and restore movement in patients paralyzed by a severe spinal cord injury, according to a small clinical trial at the Mayo Clinic. One man who was paralyzed from the neck down after a surfing accident is now able to walk again after getting stem cell therapy.

"This study documents the safety and potential benefit of stem cells and regenerative medicine," first author Mohamad Bydon, MD, a Mayo Clinic neurosurgeon, said in a press release. "In spinal cord injury, even a mild improvement can make a significant difference in that patient's quality of life."

The ten patients who participated in the Phase 1 study had adipose (fat) stem calls removed from their abdomen or thigh. After several weeks, 100 million new mesenchymal stem cells (MSCs) grown in a laboratory petri dish were injected into each patient’s lumbar spine. It’s believed the cells then migrate to the injured part of the spine. Participants were regularly followed for the next two years to assess their response to treatment.

The study findings, published in the journal Nature Communications, show that 7 of the 10 patients showed improvement based on the American Spinal Injury Association’s Impairment Scale. Improvements included increased sensation when tested with a pinprick or light touch, increased muscle strength, and the recovery of voluntary bowel function. Three patients showed significant improvement, four had a moderate improvement, and three had no response.

This Mayo Clinic video shows how the process works:

Perhaps the most dramatic improvement was in Chris Barr, a California man who was paralyzed in 2017 while surfing near San Francisco. He broke his neck in eight places when his head hit the ocean floor.

Barr was the first person enrolled in the Mayo study. Eighteen months after the stem cell injection, Barr was able to walk again and continues to show improvement in his mobility and quality of life.

"I never dreamed I would have a recovery like this," Barr told ABC News. "I can feed myself. I can walk around. I can do day-to-day independent activities."  

No serious adverse events were reported from the stem cell treatment. The most common side effects were headaches and musculoskeletal pain that went away after over-the-counter medications were taken.

Since safety is the primary goal of a Phase 1 study, further research will be needed to assess the improvements in movement and sensation. The use of fat-derived stem cells for spinal cord injury is considered experimental by the Food and Drug Administration.

According to the National Spinal Cord Injury Statistical Center, nearly 300,000 Americans currently suffer from a spinal cord injury, costing the healthcare system over $40 billion annually.  The estimated lifetime cost for each patient can reach millions of dollars.

The spinal cord has limited ability to repair itself. Patients who suffer a significant injury typically experience most of their recovery in the first six to 12 months. Improvements generally stop 12 to 24 months after an injury. Only about 5% of people who are paralyzed can expect to regain any feeling or movement.

"For years, treatment of spinal cord injury has been limited to supportive care, more specifically stabilization surgery and physical therapy," Dr. Bydon says. "Many historical textbooks state that this condition does not improve. In recent years, we have seen findings from the medical and scientific community that challenge prior assumptions. This research is a step forward toward the ultimate goal of improving treatments for patients."

‘Great Potential’ in Stem Cell Therapies for Knee Osteoarthritis

By Pat Anson, PNN Editor

Osteoarthritis of the knee is one of the most common forms of arthritis, causing progressive damage and thinning of cartilage in the knee joint.  Over 32 million American adults have knee osteoarthritis (OA), but most are treated with injections or pain medications that provide only temporary relief and often have side effects.

Could stems cells provide a more effective and long-lasting treatment for knee OA? Clinical trials have had mixed results so far, so a group of researchers in China conducted a meta-analysis of nearly 1,200 studies, weeding out the ones that were poorly designed or biased.

They eventually settled on 16 studies involving 875 patients with knee OA, most of them high quality studies that were randomized with control groups to compare results with.

Their findings, published in the Journal of Orthopaedic Research, show that stem cell treatment was associated with significant reductions in patient-reported pain from the third month onwards.

The most pain relief came from mesenchymal stem cells (MSCs) derived from a patient’s own body fat (adipose tissue) and stem cells derived from umbilical cord blood. Injections of MSCs derived from a patient’s fat provided better pain relief than stem cells from other donors and led to the most recovery of knee joint function.

“Stem cell transplantation proved safe and effective for knee osteoarthritis treatment,” the authors wrote. “Different sources of stem cells have a good effect on alleviating knee joint pain, restoring knee joint function, and minimizing patient trauma.”

The researchers said there was “great potential” for MSC therapy in the treatment of knee OA, but larger studies were needed to confirm their findings.

“The safety and efficacy of MSC therapy require rigorous validation with a larger sample size before clinical application. From the perspectives of relieving knee joint pain, promoting knee joint function recovery, and reducing patient trauma, umbilical cord‐derived stem cells should be considered as a priority option, followed by ADSCs (adipose stem cells), and finally bone marrow‐derived stem cells.”

In 2019, a small Canadian study found that stem cells collected from a patient’s bone marrow significantly reduced knee pain from osteoarthritis for as long as a year. But that study only involved 12 patients.

FDA Foot Dragging

Why are there so few good quality studies? Stem cell promoters have long complained about foot dragging by the Food and Drug Administration, which has been reluctant to approve new stem cell therapies that are not tested in randomized, double-blind, placebo-controlled studies — the so-called “gold standard” in clinical trials.

The FDA sent warning letters to 20 stem cell manufacturers and clinics in 2019, saying they were in violation of FDA guidance requiring stem cells to undergo “minimal manipulation.” The agency said the science behind stem cells made from a patient’s own tissue had not been proven 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,” then FDA commissioner Scott Gottlieb, MD, and FDA Biologics Center Director Peter Marks, MD, said in a joint statement.

Critics say the FDA is still slowing down stem cell research, despite a pledge to approve 10 to 20 cell or gene therapies annually by 2025. So far this year, the agency has only approved five.  

“Despite signs of progress and a strong commitment from FDA leadership to improve its readiness for these cutting-edge therapies, the agency remains far off pace. Its risk-averse approach and culture that’s slow to adapt to new science could become a curse for many patients and the scientific field as a whole, with investment in biotech chilling in recent quarters,” Richard Burr, a policy adviser for health and life sciences consultant DLA Piper, wrote in an op/ed published in STAT News.

Burr is a former U.S. senator and congressman from North Carolina.

“During my time in Congress, I was one of the FDA’s toughest critics, but I also fiercely defended its mission because I believe in it. The FDA now has an opportunity to transform its oversight of cell and gene therapies and deliver on promises made to patients,” Burr said.

Stem Cell Discovery Could Revolutionize Spine and Cancer Care

By Pat Anson, PNN Editor

The discovery of a new type of stem cell could revolutionize the treatment of spine disorders and slow the progression of some cancers, according to a groundbreaking study published in Nature.

Researchers from Hospital for Special Surgery (HSS) and Weill Cornell Medicine say the vertebral stem cells they found in human spines appear to play a key role in spinal health and in the metastasis of cancerous tumors as they spread through the body.

“There are two big takeaway discoveries that were made here. One is that we have discovered a stem cell that forms the spine and maintains the spine throughout life. This cell makes all the other cells that mineralize the spine,” said lead investigator Matthew Greenblatt, MD, associate professor of pathology and laboratory medicine at Weill Cornell Medicine.

“The second discovery here is that we found that this stem cell drives tumors. Breast cancer is what we focused on here, but likely also prostate cancer.”

Cancer experts have long believed that tumors metastasize to other parts of the body simply through blood flow. But Greenblat and his colleagues found that vertebral stem cells essentially attract cancer cells to the spine. That could explain why some cancers are first detected in the spine after they have metastasized from the breast, prostate and lung.

“Because we found that molecular ‘come here’ signal that's made by this spine stem cell, that gives us the ability to block that signal therapeutically. And that's something we're working on to try to prevent or treat established spine metastases,” Greenblatt told PNN.

Boosting Bone Health

Researchers say their discovery could also lead to breakthroughs in spinal health, by giving physicians a way to speed up recovery from spinal injuries and slow the progression of degenerative conditions such as osteoporosis, a disease that makes bones thinner, less dense and more likely to fracture.

For example, someone with degenerative disc disease could have their vertebral stem cells harvested, reproduced in a laboratory, and then reinjected to stimulate the growth of new bone. In animal tests, human vertebral stem cells helped laboratory mice form new bones in their spines.

“We can show that they formed basically little vertebral bones when those patient cells are put into mice, which really tells us that we found the right cell. And we can work with the cell transplant and retain stability to make new bone,” said co-author Sravisht Iyer, MD, a spine surgeon at HSS.

“I think kind of figuring out how to recruit the cells or how to how to encourage them to form more bone is going to be an important area or avenue of investigation for us, as a way to help people and protect people against what is a very morbid condition for them.”

Iyer says early treatment with vertebral stem cells could help someone with osteoporosis or a spine fracture, but wouldn’t necessarily benefit patients suffering from more advanced cases of bone loss.

“By the time people are presenting to us with spine pain, they usually have some element of compressive pathology or a degree of degeneration, which will likely require some intervention, whether that's surgery or epidural injection,” Iyer said.

“Where this work I think can really help push us forward is once you get those at-risk patients, they probably will need a surgery because a lot of degeneration is asymptomatic, and by the time they get to you they probably need something, but maybe you can prevent the second, third or fourth operation or intervention.”

More research and human studies are needed before the stem cells can be used in clinical settings to improve bone health and slow the metastasis of cancer cells. But researchers are excited by what they’ve learn so far.    

“We predict this discovery will lead to the targeting of these cells to disrupt the function and ultimately reduce the spread of cancer to the spine," said Greenblatt.

Stem Cells Could Help Diabetics Produce Their Own Insulin

By Pat Anson, PNN Editor

With insulin prices soaring out-of-reach for many U.S. patients, there’s hope on the horizon for people with Type 1 diabetes. Researchers are making significant progress in developing stem cell therapies that could restore their ability to produce their own insulin.

Interim findings from two early stage clinical trials, published today in the journals Cell Stem Cell and Cell Reports Medicine, show that pancreatic endoderm cells derived from human pluripotent stem cells (PSCs) began producing insulin in diabetic patients within months of being implanted in a tiny device under the skin.

While the amount of insulin secreted by the cells was not enough to cure Type 1 diabetes, they were sufficient enough to reduce the insulin requirements of some patients by as much as 20% and increase the amount of time spent in their targeted blood glucose range. Both studies showed that the stem cells can survive up to 59 weeks after implantation.

"A landmark has been set. The possibility of an unlimited supply of insulin-producing cells gives hope to people living with type 1 diabetes," says Eelco de Koning, MD, of Leiden University Medical Center in the Netherlands, who co-authored a commentary published in Cell Stem Cell. "Despite the absence of relevant clinical effects, this study will remain an important milestone for the field of human PSC-derived cell replacement therapies as it is one of the first to report cell survival and functionality one year after transplantation."

There are a number of caveats here. Less than three dozen patients participated in the Phase 1/2 studies, the outcomes were highly variable, and there were no control groups to compare the results with. The implanted stem cells were also derived from donors – meaning the patients had to take immunosuppressive drugs to prevent their bodies from rejecting the implants, leaving them vulnerable to infections. At least two patients experienced serious adverse events associated with having their immune systems suppressed.

Researchers still need to determine at what stage the stem cells are optimal for transplantation and the best place to implant them. It is also not clear how long the cells remain effective and whether the need for immunosuppressive therapy can be eliminated.

But the studies demonstrate that stem cells can mimic the insulin-producing pancreas cells that diabetics lack.

“A landmark has been set. The possibility of an unlimited supply of insulin-producing cells gives hope to people living with type 1 diabetes.”

— Eelco de Koning, MD

"The clinical road to wide implementation of stem cell-derived islet replacement therapy for type 1 diabetes is likely to be long and winding,” de Koning says. "But an era of clinical application of innovative stem-cell based islet replacement therapy for the treatment of diabetes has finally begun."    

About 460 million people worldwide have diabetes mellitus, a disorder in which the body does not produce enough insulin, causing blood sugar (glucose) levels to be abnormally high.  In Type 1 diabetes, the body’s immune system attacks the insulin producing cells of the pancreas. Left untreated, diabetes damages blood vessels and significantly raises the risk of stroke, heart attack and diabetic neuropathy.

Diet, exercise and regular insulin injections can help control Type 1 diabetes. But with insulin selling for about $300 a vial in the United States – 10 times more than in other developed countries --  some diabetics have rationed or even stopped taking the life-saving injections.

Another encouraging stem cell study -- involving just one patient -- was recently reported by Vertex Pharmaceuticals. A chronically ill man with Type 1 diabetes who has been taking insulin injections for decades – up to 34 units per day – began producing his own insulin after being injected with an experimental stem cell product called VX-880.

As a test, researchers only injected him with about half the targeted amount of VX-880, but within 90 days the man had reduced his need for insulin injections by 91 percent.

“These results from the first patient treated with VX-880 are unprecedented. What makes these results truly remarkable is that they were achieved with treatment at half the target dose,” Bastiano Sanna, PhD, Executive Vice President of Vertex, said in a statement. “While still early, these results support the continued progression of our VX-880 clinical studies, as well as future studies using our encapsulated islet cells, which hold the potential to be used without the need for immunosuppression.”

Vertex plans to expand the study to eventually include up to 17 patients, at multiple sites in the U.S. and Canada.

A Promising Stem Cell Therapy for Back Pain

By Gabriella Kelly-Davies, PNN Columnist

Just before sunrise on Christmas Eve last year, a delivery van from our local fish market left a bulky box of fresh prawns, oysters and lobsters on our doorstep for Christmas Day celebrations.  

Sleepily bending over, I picked up the box, unaware it was packed to the brim with enormous blocks of ice to prevent the seafood from succumbing to Australia’s stifling summer heat. As I lifted the box from the doormat, I felt a sharp pain like an electric shock run down the back of my left leg and pins and needles explode in my left foot.  

Fast forward to now, and the pain and pins and needles sensation are constant, especially when I sit to write. Like millions of other people, I have chronic lower back pain, the leading cause of disability worldwide. And like them, I too want the pain to go away without surgery.  

Two weeks ago, my pain specialist injected cortisone into my spine, reducing the pain enough to allow me to sit for meals and do a little writing. But he warned I would most likely need surgery at some point. The neurosurgeon agreed, suggesting microdiscectomy was my only option.  

As a former physiotherapist, I know that a lumbar discectomy can relieve the symptoms of nerve compression, but it doesn’t reverse the underlying degeneration of the intervertebral disc. This is why up to one third of patients continue to experience back pain after surgery and some require further operations.

In my search for non-surgical treatments, I read an article about Australian research that has led to the development of a new stem cell therapy to treat back pain. Professor Tony Goldschlager, who leads the study, is a neurosurgeon who advocates for the use of minimally invasive spinal surgery. He heads up a research team at Monash University in Melbourne that is part of the Monash Health Translation Precinct (MHTP).  

Goldschlager started his stem cell research 15 years ago. He and his team developed the stem cell therapy in the laboratory, then spent years testing it in preclinical models. The results of several studies revealed that the therapy was safe and effective. After completing these studies, the researchers began human clinical trials, testing the ability of stem cells to regenerate the intervertebral disc and reduce back pain.  

“We’ve had success both in preclinical and clinical studies of being able to restore structure and function of the disc,” Goldschlager told me. “This reduces pain and improves quality of life for patients.” 

Phase Two clinical trials saw a significant number of patients report reduced back pain for up to two years after a single injection. Phase Three trials are almost complete and while Goldschlager hasn’t received all the results from overseas studies, the data he has seen so far is promising. He is hopeful the new treatment— a single injection — will be available in two years after the final round of clinical trials concludes. 

“What excites me is that we might be able to prevent surgery all together and regenerate the disc. Most of the current treatments don’t address the underlying problem. But the stem cell injection reduces the inflammation and stimulates a regenerative process in the disc, removing the source of back pain. The stem cells can become new disc-like cells and replenish the damaged disc cells,” explained Goldschlager. 

During the last 15 years, Goldschlager and his team have published the results of their studies in peer-reviewed journals such as Spine, Nature Outlook and the Journal of Neurosurgery. In 2015, they published an extensive review of the use of stem cell therapies in lumbar disc disease. 

New Era in Medicine

While the use of stem cells heralds the dawn of an exciting new era in modern medicine, it also raises several ethical and safety concerns. Critics say many stem cell therapies are unproven, and others believe it is unethical to destroy human embryos during research or create new embryos specifically for research. 

Goldschlager is acutely aware of these concerns and in 2010 as a neurosurgery registrar, worked in a research team that published an article on the ethics of using stem cell therapies in patients with spinal cord injuries. He says the therapy his team has developed doesn’t raise ethical concerns because it is based on a proprietary adult stem cell technology from Mesoblast, an Australian biotechnology company.

The cells are derived from the bone marrow of healthy young adults who have given informed consent. Young adults are selected because the number of stem cells in our bodies reduce as we age. The cells of older people are also less effective at repairing damaged tissues and organs.

Commercial stem cell clinics usually harvest the fat, muscle or cartilage cells of their patients, process the cells in a centrifuge, then inject them back into the same patient’s body. This yields a mixed population of cells with a small and inconsistent number of stem cells. Adults of all ages are offered this treatment, even though it might not work for older patients because their stem cells are not as plentiful or robust as those of younger ones. These treatments can cost thousands of dollars, are often ineffective, and come with a heightened risk compared to a pure, tested proprietary off-the-shelf product.  

Another reason for caution is that some of the clinicians who provide stem cell treatments lack sufficient training and accreditation, increasing the risk of safety and efficacy issues. It is critically important for patients to check the qualifications of clinicians who offer stem cell therapies and to understand how the cells used at these clinics are created. The therapy should have been through rigorous clinical trials to demonstrate safety and efficacy.  

While new stem cell treatments offer hope to millions of people who live with degenerative spinal conditions, they are not a “miracle cure.” Still, I hope I’ll have the option of trying Professor Goldschlager’s technique once it is available.

Gabriella Kelly-Davies lives with chronic migraine.  She recently authored “Breaking Through the Pain Barrier,” a biography of trailblazing Australian pain specialist Dr. Michael Cousins. Gabriella is President of Life Stories Australia Association and founder of Share your life story.

Study Finds ‘Urgent Need’ for Regulation of Stem Cell Industry

By Pat Anson, PNN Editor

Over 2,750 businesses and clinics in the U.S. are selling stem cell products – four times as many as in 2016 – most of them offering treatments for pain and orthopedic conditions that are not approved by the Food and Drug Administration, according to a new analysis.

The only stem cell products that are currently approved by the FDA are used to treat sickle cell disease and some cancers. Despite FDA threats to crackdown on “unproven” stem cell products, clinics have proliferated around the country, marketing stem cell therapies for chronic pain, arthritis and other medical conditions. California, Texas and Florida lead the nation with over 300 stem cell clinics in each state.

"One of the most troubling features of this marketplace is that businesses selling unproven and non-FDA-approved stem cell products often use marketing misrepresentations and aggressive sales tactics to exploit the hope, suffering, fear or desperation of patients," says lead author Leigh Turner, PhD, a professor of health, society and behavior at the University of California, Irvine.

Using Google Maps and other online search tools, Turner and his colleagues spent five years compiling data on stem cell businesses. Their findings are published online in the journal Cell Stem Cell.

Turner's analysis found that the most common types of stem cell treatments being offered were for pain (85%), orthopedic diseases and injuries (46%), and sports-related injuries (22%). Most companies did not disclose on their websites how much their therapies cost, but of those that do, the average price was $5,118. Stem cell injections and infusions are usually not covered by insurance.

"Many of these 'clinics' are promoting unlicensed and unproven stem cell products and claim their interventions do not require FDA approval," Turner said. "However, that couldn't be further from the truth. I found that there is widespread promotion of products that do, in fact, require premarketing authorization by the FDA. In many cases, these clinics are using misleading advertising and predatory marketing techniques."

Most stem cell businesses offer “autologous” stem cell products derived from a patient’s own body tissue – such as fat or bone marrow -- which the companies don’t consider a “drug” that falls under FDA jurisdiction.

The FDA has been slow to take action against unlicensed stem cell operators, due in part to a grace period the agency adopted in 2017 to give them more time to submit new drug applications for FDA review. That grace period recently ended, with no indication that many stem cell providers took the agency up on its offer.      

Turner acknowledges there have been “some encouraging results” from studies on stem cell treatments for osteoarthritis and orthopedic conditions, but said there was not enough research yet to justify commercializing them. He worries the stem cell industry has grown so quickly that the FDA can’t provide adequate regulation without substantial increases in enforcement activity.

“There is an urgent need for better oversight of this marketplace. Regrettably, marketing claims by some businesses also question the legitimacy and trustworthiness of regulatory bodies,” he wrote.

Turner’s research was funded by The Pew Charitable Trusts, which released its own report in June that was highly critical of the stem cell industry. Like the Pew report, Turner cites cases where patients suffered injuries after receiving unapproved stem cell treatments, without pointing out that the number pales in comparison to over 250,000 Americans who die every year from medical errors linked to “proven” treatments.   

Researchers Warn of Serious Risks in ‘Unproven’ Stem Cells

By Pat Anson, PNN Editor

A new study is warning patients and healthcare providers of possible bacterial contamination and other serious risks in “unproven” stem cell products being marketed as treatments for chronic pain, arthritis and other medical conditions.   

The study findings, published in JAMA Network Open, are the outcome of an investigation that began in 2018 after public health officials began receiving reports of bacterial infections in stem cell patients. At least 20 patients in eight states developed serious infections after receiving stem cells derived from umbilical cord blood.

All of the infections were traced back to a single stem cell manufacturing lab in California, where over half the samples tested by the CDC were found to be infected with E coli and other bacteria. The contaminated products were recalled and the lab was ordered to improve its infection control procedures, but researchers say the risk of another outbreak remains.

“The findings from this outbreak underscore that unapproved and unproven stem cell products can expose patients to serious risks without clear benefit, including the possibility of product contamination,” wrote lead author Kiran Perkins, MD, an epidemiologist at the CDC Division of Healthcare Quality Promotion. “Patients and health care practitioners who are considering the use of unapproved products marketed as stem cell treatment should be aware of their unproven benefits and potential risks, including serious infections.”

The only stem cell products that are currently approved by the Food and Drug Administration are derived from umbilical cord blood, which are used to treat sickle cell disease and some cancers.

Despite FDA threats to crackdown on unproven stem cell treatments, over a thousand clinics have opened around the country, promoting stem cell injections and infusions to treat a wide variety of diseases and injuries. Many use stem cell products derived from a patient’s own body tissue – such as fat or bone marrow -- which clinic operators don’t consider a “drug” that falls under FDA jurisdiction.

Researchers say the clinics are taking advantage of desperate patients who want quick solutions to complex medical problems.

“Hundreds of clinics across the US unlawfully advertise stem cell treatments to patients as a cure for a variety of conditions for which there are currently no effective medical treatments, including certain neurological disorders, autism, and aging. Although some patients may be willing to risk unproven stem cell treatment over surgery for conditions such as chronic pain and degenerative joint diseases, this investigation demonstrates the potential risk associated with the use of these products,” Perkins and her colleagues wrote.

“Manufacturers of unlicensed products, such as those associated with this outbreak, violate the law for profit at the expense of public health. Many create market confusion by erroneously describing their products as novel therapies that do not require FDA premarketing review or approval. That is not the case.”

Of course, just because a treatment is unapproved or unlicensed doesn’t mean it’s ineffective. There are numerous examples of stem cells being used successfully to treat serious neurological conditions such as arachnoiditis and paralysis. Professional athletes have also embraced stem cells and platelet injections as therapies for stubborn muscle and joint injuries, often traveling overseas for treatments they can’t get in the U.S.

The FDA has been slow to take action against stem cell clinics and manufacturers, due in part to a “grace period” the agency adopted in 2017 to give them more time to submit new drug applications for FDA review. The grace period ended in May 2021, with no indication that many stem cell providers took the agency up on its offer.      

A recent report from the Pew Charitable Trust identified 360 patients who had adverse events involving stem cells over a 17-year period. While that pales in comparison to the number of Americans who die every year from medical errors -- over 250,000 --  Pew said it was time for “increased FDA enforcement action” against stem cell clinics.

Experimental Implant Repairs Joints With Cartilage Made From Stem Cells

By Pat Anson, PNN Editor

An experimental implant containing cartilage derived from stem cells reduced pain and restored function in dogs with damaged hip joints -- a study that researchers say could be a significant step towards repairing and replacing cartilage in humans with osteoarthritis.

Osteoarthritis is a progressive joint disorder caused by painful inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine.

“One of the holy grails of orthopedics is to replace cartilage, but there hasn’t been an effective way to do it,” says co-author Duncan Lascelles, PhD, a professor of surgery and translational pain research and management at North Carolina State. “Most of the focus is on replacing or restoring the cartilage surface with artificial materials, but regenerating cartilage isn’t possible right now. And many of the artificial products in use don’t integrate with the body.”

Lascelles and his colleagues developed a cartilage repair implant using a textile manufacturing process that utilizes three-dimensional (3D) weaving with composite material. When seeded with a patient’s own stem cells, the “bioartificial” implant is designed to integrate with native bone while preserving the integrity of the joint.

“Combining 3D printing with advanced textiles enabled us to engineer an implant that mimics the function of native, healthy tissues in the joint from day one after implantation,” said co-author Bradley Estes, PhD, President of Cytex Therapeutics, which developed the implant technology. “We also designed it to dissolve over time so that, ultimately, joint function is transferred back to the patient’s own tissues during the healing process.”

The researchers used the implant to resurface damaged hip joints in dogs. Cartilage derived from stem cells was first allowed to grow on the implant for several weeks before surgery, then the implant was placed into the damaged area of the dogs’ joints. Over time, the implant dissolved, leaving only the dog’s own natural tissue in the repaired hip joint.

Four months after surgery, researchers say dogs that received the cartilage implant returned to baseline levels for both pain and function, while dogs in a control group never improved. They also saw evidence that the implant had successfully integrated into the hip joints, effectively resurfacing them.

“We were thrilled that the implant was so effective at restoring the activity levels of the animals,” Estes says. “After all, this is why patients go see their physicians – they want to be able to play tennis, play with their kids, and, in general, re-engage in a pain-free active lifestyle that had been taken away by arthritis.”

While osteoarthritis primarily affects older adults, researchers hope the experimental implant will address some of the problems associated with total joint replacements in younger, active patients.

“There are significant drawbacks to total joint replacements in the young patient,” Lascelles says. “The surgery is more complicated, and the artificial joints are only good for a particular number of years until they must be replaced, often with poorer results each time.

“This procedure is less invasive, and the implant uses the body’s own cells and integrates into the damaged area with little danger of rejection. We believe that it is an early intervention that could be a major advance in postponing joint replacements for dogs and hopefully one day for humans.”

The research findings are published online in Science Advances. The study was funded by Shriners Hospitals for Children, the Arthritis Foundation, the Nancy Taylor Foundation for Chronic Diseases, and the National Institutes of Health.

Pew Cherry-Picked Patient Cases in Stem Cell Report

By A. Rahman Ford, PNN Columnist

As a self-professed vehicle for public policy-making, the Pew Charitable Trusts has released a new report that aims to protect Americans from the harms of “unapproved” stem cell therapy.

Regrettably, the 34-page report relies on cherry-picking of patient cases, supports an aggressive crackdown on stem cell clinics by the FDA, and curiously take the undemocratic position of supporting online censorship.

Like a similar report in 2019, Pew’s stated intent is a noble and valuable one: to protect patient health. The new report correctly asserts that “stem cell products and other regenerative therapies have significant potential to treat traumatic injuries and serious diseases.” Unfortunately, what follows is a porous analysis that includes woefully unsubstantiated assumptions and misdirected conclusions.

To support its claims of an ever-increasing number of harmful “adverse events” resulting from unapproved stem cell treatments, Pew researchers looked at peer-reviewed journals, government and news media reports, the FDA’s adverse event reporting system, and online consumer reviews of stem cell businesses from 2004 to 2020.  

Over this 17-year period, Pew identified 360 people who had adverse events involving stem cells. Most of the adverse events (AEs) were relatively minor, such as bacterial infections, but some were serious enough to result in blindness, organ damage or even death. While each case is regrettable, keep in mind that over 250,000 people in the U.S. die every year from medical errors.

The Pew report assumes that adverse events from stem cells are under-reported, but provides no evidence for this claim. On the basis of the cases found, Pew concludes that “increased FDA enforcement action” against stem cell clinics is needed. The report also calls on state agencies, state legislatures and professional organizations to get involved.

Less Than Definitive Definitions

On its face, Pew’s evidence against stem cells seems somewhat convincing. But upon closer inspection, it has serious and alarming methodological flaws.

First, the report’s definitions are problematic. For example, Pew defines an adverse event as “any undesirable experience associated with the use of a medical product in a patient.” This definition is so broad it can encompass almost anything. Furthermore, it’s conceptually clumsy to equate “adverse” with “undesirable” – the two are simply not the same in medicine, academia, policy, or in simple common sense.

To make matters worse, Pew conflates “unproven” therapies with “unapproved” therapies, when the two are very different. “Unapproved” means it’s not FDA-approved, which covers most products offered by stem cell clinics. Thai’s fine. But Pew then asserts that the stem cell products are also “unproven” because they lack “definitive, high quality evidence of safety and efficacy.”

To assert that stem cells products such as stromal vascular fraction (SVF) and autologous mesenchymal stem cells are all “unproven” simply defies the reams of published studies to the contrary. There are many examples where stem cell therapies were “proven” to safely and effectively help people, even when they are not FDA-approved.

And the “safe and effective” products the FDA has approved harm people all the time. Thus, the question remains, if “unproven” and “unapproved” are going to be used interchangeably, as the Pew report admits, then what is the point of having definitions in the first place?

Cherry-Picked Cases

Second, the Pew report wrongly assigns all cases equal evidentiary weight, regardless of the source from which they were collected.

Is it methodologically honest to give a case from a peer-reviewed academic journal the same scientific and evidentiary value as a case found on Yelp, a website where people go for reviews of Philly cheesesteaks and fish tacos? And how exactly did Pew investigate the veracity of posts it found on Facebook and Google? It didn’t.

Pew concedes that its social media analysis did not find “many new serious or life-threatening” adverse events. It also acknowledges that not all the consumer reviews about stem cells were negative, stating that “many, in fact, were positive.” Pew’s analysis excluded the positive reviews because it didn’t consider them reliable, but inexplicably included the negative ones. Why?    

Could it be that Pew was only looking for data that supported a conclusion that it had already arrived at?  If so, that would be unprofessional, unscientific and very, very troubling.

To cherry-pick some opinions over others is also undemocratic. This would be ironic because on its website, Pew purports to “invigorate civic life by encouraging democratic participation and strong communities.” Pew also maintains that it is inspired by America’s Founding Fathers and their belief in “the importance of an informed democracy.”

Given the report’s skewing of data, perhaps for Pew it’s only democracy for some.

This conclusion would coincide with Pew’s continued urging of online media platforms to censor stem cell information it finds disagreeable. In its report, Pew implores “companies that manage online platforms [to] do more to limit the spread of misinformation, and prevent clinics from advertising their products on their platforms.”

Pew would do well to realize that speech – online or otherwise – is a constitutionally protected freedom, and the perimeter of the public square should not be circumscribed so as to serve unspoken agendas.

All in all, the Pew report’s lack of methodological rigor undermines much of its credibility. To be sure, when any American is harmed by any medical procedure it should be taken seriously. And most stakeholders agree that reasonable regulations and enhanced data collection are welcome.

But the Pew report ignores the critical point that the current FDA regulatory scheme for stem cells is unduly burdensome and in desperate need of change. Cracking down on stem cell clinics won’t solve the problem of chronic pain, and it won’t solve the problem of pills and surgeries that don’t work, harm or kill. All it will do is discriminate against persons with disabilities and poor people. It doesn’t get more undemocratic than that.

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

Pilot Study Shows Stem Cells Effective in Treating Shoulder Pain

By Pat Anson, PNN Editor

A single injection of stem cells has shown promise as a treatment for shoulder pain caused by rotator cuff disease, according to the results of a small pilot study conducted by the Kessler Foundation.

Ten wheelchair users with moderate to severe shoulder pain received an injection of adipose stem cells derived from their own fat tissue. The participants all had spinal cord injuries and chronic shoulder pain for at least six months that did not respond to conventional treatment.   

The stem cells were micro-fragmented using minimal manipulation to preserve fat clusters and the cells’ regenerative properties. This micro-fragmented adipose tissue (MFAT) was then injected into shoulder tendons under ultrasound guidance.

The study findings, recently published in the Journal of Spinal Cord Medicine, showed nearly 80 percent of participants had a significant decrease in pain symptoms, and all but one reported improvement in pain and function. Symptoms steadily improved over the course of a year, suggesting the injections have long-lasting effects. There were no significant adverse events.

"These results show that the minimally invasive injection of micro-fragmented adipose tissue is a safe and efficacious option for wheelchair users with shoulder pain caused by rotator cuff disease," said Gerard Malanga, MD, a founder of the New Jersey Regenerative Institute and a visiting scientist at the Kessler Foundation.

“We feel there is great potential for this therapy to help people with shoulder pain manage their symptoms and improve their quality of life.”

In addition to their regenerative properties, MFAT stem cells are believed to provide cushioning and to fill-in structural defects when injected into damaged shoulder joints.

Malanga and his colleagues are currently conducting a larger Phase 2 controlled study with 24 participants that will compare MFAT injections to corticosteroid injections for treating pain caused by rotator cuff disease or tears.        

Shoulder pain is a common occurrence among wheelchair users with spinal cord injuries because they rely solely on their upper limbs to perform everyday tasks. The pain is often caused by soft-tissue injuries such as inflamed rotator cuff tendons. Pain medication and physical therapy are typically used to treat shoulder pain, with surgery as a last resort – not a good option for someone with a spinal cord injury.

The New Jersey-based Kessler Foundation is a global leader in rehabilitation research and employment programs for people with neurological disabilities caused by diseases and injuries of the brain and spinal cord.

Positive Results From Stem Cell Trial for Knee Osteoarthritis

By Pat Anson, PNN Editor

A California stem cell company has announced positive results from a small, early-stage clinical trial of an experimental stem cell therapy for knee osteoarthritis.  

The Phase 1/2a trial conducted by Personalized Stem Cells (PSC) involved 39 patients with knee osteoarthritis who were given a single injection of autologous mesenchymal stem cells derived from their own body fat. Safety was the primary objective of the trial and there were no serious adverse events reported by the company.

The secondary objective of the trial was to assess the effectiveness of the therapy with the Knee Injury and Osteoarthritis Outcome Score (KOOS), a survey that asks patients about their pain, other symptoms, daily function, quality of life, and recreational activities. Nearly 80% of study participants improved above the “minimal important change” (MIC), with an average improvement over baseline of 2.2 times the MIC.

Osteoarthritis is a progressive joint disorder caused by painful inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine.

Results from the PSC study have been submitted to the FDA for review. The company hopes to get approval for a larger, Phase 2 randomized study of its stem cell therapy later this year.  

“We are pleased at the strong safety profile and efficacy results in this FDA-approved clinical study of stem cell therapy for knee osteoarthritis,” said PSC founder and CEO, Dr. Bob Harman. “We are proud to have reached this milestone in our first FDA approved clinical trial. This data supports our progress in the larger placebo-controlled clinical study.”

Veterinarians Already Using Stem Cells

While the FDA has approved hundreds of clinical trials of stem cells, it has not approved a single stem cell product as a treatment for arthritis or any orthopedic condition. That hasn’t stopped stem cell clinics from offering regenerative medicine to patients or veterinarians from using it on animals.

VetStem Biopharma, the parent company of PSC, pioneered the use of adipose derived stem cells in veterinary medicine. Its laboratory has processed stem cells for nearly 14,000 dogs, cats, horses and other animals for use by veterinarians in the U.S. and Canada.

“The 15 years of veterinary experience with adipose derived stem cell therapy of our parent company, VetStem Biopharma, provided the basis for our FDA study submission and approval and provided valuable insights into the study design and conduct,” said Harman.

In addition to the Phase 2 trial for osteoarthritis, PSC plans to pursue FDA approval for a stem cell trial to treat traumatic brain injuries in humans. A clinical study using PSC’s stem cell platform to treat respiratory distress syndrome in COVID-19 patients is currently underway.

Stem Cells Restore Function in Patients Paralyzed by Spinal Cord Injuries

By Pat Anson, PNN Editor

Intravenous injection of mesenchymal stem cells (MSCs) in patients paralyzed by spinal cord injuries led to significant improvement in their motor functions, according to a team of researchers at Yale University and Sapporo Medical University in Japan.

The study findings, published in the Journal of Clinical Neurology and Neurosurgery, focused on 13 patients who suffered spinal cord injuries (SCIs) after falls or trauma. Some lost the ability to use their arms and legs, while others suffered coordination and sensory loss, or experienced bowel and bladder dysfunction.

For more than half of the patients, substantial improvements in motor function were observed within weeks of being injected with autologous MSCs derived from their own bone marrow. Although this was a small observational Phase 2 study, researchers are excited by the findings.

"The idea that we may be able to restore function after injury to the brain and spinal cord using the patient's own stem cells has intrigued us for years," said senior author Stephen Waxman, MD, a professor of neurology, neuroscience and pharmacology at Yale. "Now we have a hint, in humans, that it may be possible."

One of the patients profiled was a 34-year-old man who was left partially paralyzed and bedridden after a fall. He received an intravenous injection of MSCs 47 days after his injury. Two weeks after the infusion, voluntary movement was restored to his lower extremities and he was walking with the support of a walker.

In another case, a 47-year-old man left bedridden after a diving accident showed rapid improvement after a stem cell infusion. He was able to drive a wheelchair the next day, walk and climb stairs after two weeks, and eat independently after eight weeks.

Other patients paralyzed after similar injuries were able to breath again without assistance, regain control of their bowel functions, and perform independent living tasks such as dressing and grooming.

“Although this initial case study was unblinded and uncontrolled, the SCI patients appeared to demonstrate a tendency of relatively rapid improvement of neurological function that was often apparent within a few days following infusion of MSCs,” researchers said.

“We would emphasize that this case series describes an early study on a small number of patients. In addition to being unblinded and uncontrolled, this study has a number of limitations. We cannot rule out observer bias nor a contribution of surgical intervention to recovery in cases where this intervention occurred, or spontaneous recovery.”

Other case studies have also shown that stem cells can restore motor and sensory function in patients paralyzed by spinal cord injuries.

The Mayo Clinic reported in 2019 that a California man paralyzed from the neck down in a surfing accident was able to walk again after being injected with his own stem cells. Researchers emphasized the man was a “super-responder” and that other paralyzed patients injected with stem cells don’t have such a dramatic recovery.

According to the National Spinal Cord Injury Statistical Center, over 17,000 Americans suffer spinal cord injuries each year. Chronic pain is a serious problem that can result from SCI, affecting about two-thirds of patients, with one out of three reporting their pain as severe.

Promising Results for Stem Cell Treatment of Degenerative Disc Disease

By Pat Anson, PNN Editor

An Australian regenerative medicine company has released positive results from a Phase III randomized trial showing that a single injection of its proprietary stem cell product can provide long-term relief for people with chronic lower back pain caused by degenerative disc disease.

Mesoblast Limited said the results are so promising it plans to meet with the U.S. Food and Drug Administration to discuss ways to accelerate approval of the drug as a treatment that reduces the use of opioid pain medication.

The company’s stem cell product -- remestemcel-L -- has been under development for several years. It uses mesenchymal precursor cells taken from the bone marrow of healthy donors to reduce inflammation by inhibiting the production of pro-inflammatory cytokines by white blood cells.

Sixty percent of the patients in the clinical trial who were injected with remestemcel-L reported minimal or no pain after 12 months. After 24 months, 54 percent reported little or no pain, with the greatest pain reduction in patients in the early stages of degenerative disc disease. Many patients also significantly reduced their use of opioids during the study period.

“The durable pain reduction for at least two years from a single administration indicates that rexlemestrocel-L has the potential to change the treatment paradigm for chronic low back pain due to inflammatory disc disease, a condition that affects as many as seven million patients across the United States and Europe, and to prevent or reduce opioid use and dependence,” Dr. Silviu Itescu, CEO of Mesoblast, said in a statement.

Over 400 patients were enrolled in the Phase III trial, which was conducted at 48 sites around the world, mostly in the United States. Although Mesoblast told physicians and patients not to change any medications during the trial, after 24 months there was a 40% reduction in opioid use in patients injected with rexlemestrocel-L. Those who were given a placebo saline injection increased their daily opioid consumption.

In a previous study of patients with chronic lower back pain who did not respond to conventional treatment, a single injection of remestemcel-L also reduced pain for at least two years.

The FDA has prioritized the development of new pain treatments that reduce the use of opioids. Although the agency has taken a dim view of some stem cell therapies as “unproven and potentially dangerous,” Mesoblast believes the FDA will be more open-minded about its rexlemestrocel-L treatment. Last year the agency approved an investigational new drug application for rexlemestrocel-L as a therapy for COVID-19.

“We now have two studies that show significant pain reduction and we’re fully prepared to have a discussion with FDA on a path forward,” said Mesoblast Chief Medical Officer Dr. Fred Grossman. “We’re going to get into discussions to see if there’s an accelerated path. Or, if we do need to do another study, we now have a very defined patient population where we see significant pain reduction.”

New Drug Could Improve Effectiveness of Stem Cell Therapy

By Pat Anson, PNN Editor

Scientists have developed an experimental drug that can lure stem cells to damaged tissues and help them heal -- a discovery being touted as a major advancement in the field of regenerative medicine.

The findings, recently published in the Proceedings of the National Academy of Sciences (PNAS), could improve the effectiveness of stem cell therapy in treating spinal cord injuries, stroke, amyotrophic lateral sclerosis (ALS), Parkinson’s disease and other neurodegenerative disorders. It could also expand the use of stem cells to treat conditions such as heart disease and arthritis. 

“The ability to instruct a stem cell where to go in the body or to a particular region of a given organ is the Holy Grail for regenerative medicine,” said lead author Evan Snyder, MD, director of the Center for Stem Cells & Regenerative Medicine at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, CA. “Now, for the first time ever, we can direct a stem cell to a desired location and focus its therapeutic impact.”

Over a decade ago, Snyder and his colleagues discovered that stem cells are drawn to inflammation -- a biological “fire alarm” that signals tissue damage has occurred. However, using inflammation as a therapeutic lure for stem cells wasn’t advisable because they could further inflame diseased or damaged organs, joints and other tissue.

To get around that problem, scientists modified CXCL12 -- an inflammatory molecule that Snyder’s team discovered could guide stem cells to sites in need of repair— to create a drug called SDV1a. The new drug works by enhancing stem cell binding, while minimizing inflammatory signals.

“Since inflammation can be dangerous, we modified CXCL12 by stripping away the risky bit and maximizing the good bit,” Snyder explained. “Now we have a drug that draws stem cells to a region of pathology, but without creating or worsening unwanted inflammation.”

To demonstrate its effectiveness, Snyder’s team injected SDV1a and human neural stem cells into the brains of mice with a neurodegenerative disease called Sandhoff disease. The experiment showed that the drug helped stem cells migrate and perform healing functions, which included extending lifespan, delaying symptom onset, and preserving motor function for much longer than mice that didn’t receive the drug. Importantly, the stem cells also did not worsen the inflammation.

Researchers are now testing SDV1a’s ability to improve stem cell therapy in a mouse model of ALS, also known as Lou Gehrig’s disease, which is caused by a progressive loss of motor neurons in the brain. Previous studies conducted by Snyder’s team found that broadening the spread of neural stem cells helps more motor neurons survive — so they are hopeful that SDV1a will improve the effectiveness of neuroprotective stem cells and help slow the onset and progression of ALS. 

“We are optimistic that this drug’s mechanism of action may potentially benefit a variety of neurodegenerative disorders, as well as non-neurological conditions such as heart disease, arthritis and even brain cancer,” says Snyder. “Interestingly, because CXCL12 and its receptor are implicated in the cytokine storm that characterizes severe COVID-19, some of our insights into how to selectively inhibit inflammation without suppressing other normal processes may be useful in that arena as well.”

Snyder’s research is supported by the National Institutes of Health, U.S. Department of Defense, National Tay-Sachs & Allied Disease Foundation, Children’s Neurobiological Solutions Foundation, and the California Institute for Regenerative Medicine (CIRM).

“Thanks to decades of investment in stem cell science, we are making tremendous progress in our understanding of how these cells work and how they can be harnessed to help reverse injury or disease,” says Maria Millan, MD, president and CEO of CIRM. “This drug could help speed the development of stem cell treatments for spinal cord injury, Alzheimer’s, heart disease and many other conditions for which no effective treatment exists.”