Helping the Body Repair Itself

Georgia scientists focus on the future of cell therapy.
Georgia Trend October 2021 Regen Med Malcolm Mitchell p046
Managing Pain: Former UGA and NFL football player Malcom Mitchell, founder and CEO of Share the Magic Foundation and children’s book author Credit: Ben Rollins

Regenerative medicine is booming these days because one thing this relatively new field has done well is generate a lot of buzz. Often associated with stem cells, it’s the branch of medicine devoted to repairing, replacing or regrowing damaged or diseased tissues, cells or organs. An online search turns up scores of academic institutions involved in regenerative medicine research and countless medical practices advertising its benefits. As a result, people who live with arthritis, heart disease, stroke and other conditions are eagerly clamoring for these next-gen solutions. But in some cases their expectations have gotten ahead of the treatments’ proven effectiveness.

Scientists at several of Georgia’s research institutions are working to separate fact from fiction and their investigations are revealing hope for regenerative medicine’s potential.

At University of Georgia (UGA), the Regenerative Bioscience Center (RBC) has spent more than 15 years pursuing stem cell therapies, tissue engineering and the use of blood products to treat devastating diseases. The RBC brings together collaborators from the Georgia Research Alliance, Georgia Tech, Georgia State University, Augusta University and Emory University to not only increase the knowledge and technology development around regenerative medicine, but also to help attract research funding.

More than 40 RBC scientists are focused on the full gamut of regenerative medicine research, from understanding how worms regrow parts of their bodies to commercializing the manufacturing of neural stem cells that can be used to treat diseases like Alzheimer’s and Parkinson’s.

“Now a lot of effort is focused on figuring out how to take our [body’s] own ability to repair itself and pump up our ability to regenerate tissue,” says Steven Stice, RBC director, professor and Georgia Research Alliance eminent scholar. “In many cases, regenerative medicine doesn’t mean transplanting stem cells, but understanding how stem cells in the body work to repair the body faster.”

Reducing Inflammation

According to Stice, much of regenerative medicine research is focused on reducing inflammation in specific areas of the body and it has applications for Alzheimer’s, Parkinson’s disease, arthritis, even diabetes. “Creating an environment that is non-inflamed, all the mechanisms can be there to help repair and regenerate that tissue,” he says.

More than 100 different types of arthritis exist, but what they have in common is inflammation in the joints, which causes pain, stiffness and swelling. The Arthritis Foundation recognizes several regenerative medicine treatments that may have value for pain relief, including stem cell therapies and platelet injections. The foundation’s website cautions, however, that there is no evidence stem cells can restore lost joint tissue or cause cartilage to grow.

“Most of the patients we talk to want something to bring their joint health back,” says Jason Kim, vice president of osteoarthritis research at the Arthritis Foundation, “and most people think of that as bringing their cartilage back. There are a few drugs out there in clinical trials that have been shown to bring back some cartilage, it’s just that they haven’t gotten FDA [Food and Drug Administration] approval. If you grow back cartilage but you still have pain [in the joint], have you really treated the disease?”

Much of the foundation’s research support of regenerative medicine is concentrated on treatments that have the potential to reduce pain and inflammation. A widely performed procedure for joint pain relief is platelet-rich plasma (PRP). It involves drawing a patient’s blood, spinning it in a centrifuge to separate the platelets, then injecting the platelets back into a problem joint. PRP is thought to boost the body’s natural response to inflammation and it has been shown to provide symptomatic relief lasting three to six months. Kim says TRICARE services, the military’s health program and government-managed health insurance, have approved PRP for treating knee pain but “I think we’d still love a lot more clinical research before the Arthritis Foundation can get behind it.”

Another procedure involves injecting stem cells into painful joints to stimulate the production of anti-inflammatory proteins and growth factors. Evidence exists that the procedure is safe, helps reduce pain and increases joint function. The question is: What source of stem cells – bone marrow, umbilical cord or fat – is most effective?

Kim believes one of the best clinical trials studying the question is taking place at Atlanta-based Emory Orthopaedics & Spine Center in collaboration with Georgia Tech, Sanford Health, Duke University and the Andrews Institute. The Marcus Foundation-funded trial began enrolling participants in 2019 and met its goal of 480 in June. About 25% of those participating are from Georgia. The trial is designed to help provide new standards of care using stem cells as treatment options, reveal which people are likely to have positive results with their own cells and identify the attributes needed to manufacture third-party stem cells for effective outcomes.

The trial hasn’t made results available yet, but Hicham Drissi, professor, vice chair of orthopaedic research at Emory University School of Medicine and scientific program director for the study, says the procedures “have been shown to be very safe with no major adverse events reported.” Results should be available next year.

“Our goal is to provide nonsurgical means for patients that suffer from knee arthritis but are not ready for a knee replacement,” he says. “Our unbiased research strategy will hopefully help physicians and patients determine choices of appropriate stem cell products that would effectively slow down or perhaps halt disease progression.”

Restoring Function

Athletes have turned to these types of regenerative medicine treatments for sports injuries. In fact, they have helped drive the field forward.

Valdosta native Malcolm Mitchell, a former football player who today is a children’s book author and founder and CEO of the Share the Magic Foundation literacy nonprofit, tried regenerative medicine treatments to prolong his playing years. As a UGA wide receiver from 2011 to 2015, Mitchell underwent several surgeries for ligament and cartilage damage. To help his knee pain following the surgeries, he tried PRP injections, but they had little effect. In 2014 he turned to injections of his own stem cells and his body had a positive response. He continued the treatments and finished his UGA career with accolades. The treatments also helped him play for three touchdown-filled years – and bring home a Super Bowl ring – with the New England Patriots.

“Stem cell doesn’t regenerate cartilage,” he says. “I still battle with those issues. But the overall pain subsided enough for me to compete.”

Mitchell stresses that the stem cells are not a quick fix. After they were injected it took a couple of months for them to kick in and begin reducing inflammation and pain in his knee.

“That was all I needed,” he says. “Once you go through a surgery, you’re never going to be the same. If you can decrease the pain and inflammation – or the pain from the inflammation – you’re likely to get back [to functionality] as close as possible. If stem cell [treatments] solve that issue, then hard work and dedication have to do the rest.

“I think stem cells let you manage that pain better than anything else I’ve come in contact with,” he adds, “and I tried everything up until 2019 when I decided to retire.”

For stroke victims, regenerative medicine could also be a game changer. Two years ago, Augusta University surgeons were among the first in the U.S. to inject stem cells into a patient’s brain to help restore functions lost to stroke. The procedure was done six to 12 months after the stroke to allow the brain time to heal as much as possible. Previous procedures in the United Kingdom helped stroke patients regain some functions.

Researchers are also studying whether using stem cell byproducts following a stroke can reduce inflammation, protect the brain’s nerve cells from further injury and help it regenerate tissue. One of four biotechnology startups Stice has founded out of his UGA lab, Aruna Bio, is close to clinical trials on cell components called exosomes that have the potential to check all three boxes. He uses a military analogy to explain the process.

“The stem cell is like the aircraft carrier going into battle,” he says. “It has these fighter jets that can go into small places that need to be addressed. What really does the work are these fighter jets – the exosomes that come from the stem cells.” He says Aruna Bio is able to manufacture trillions of exosomes from stem cell cultures. Results from the clinical trial should be available within five years.

Veterinary Success

One advantage the RBC has is that veterinarians are participating in its research. For example, Stice’s work with exosomes came about after promising outcomes occurred in pigs that had experienced strokes. And UGA veterinary surgeons have used stem cells taken from the recipient and multiplied in the RBC lab to help cats better accept kidney transplants.

John Peroni, UGA professor of large animal surgery and RBC co-chair, says veterinarians have been incorporating blood-derived products like PRP and tissue-derived stem cells to treat animals for about 20 years. “We’ve been in a very lucky position because we are less restricted [from a regulatory standpoint],” he says. “We can do things a bit more on the forefront than human medicine can. So for that reason, it’s been a little easier to get on with it earlier than our human counterpoints.”

Linda Delarios, owner of Cottage Hill Farm in Cumming, turned to regenerative medicine in 2018 after one of her show horses, 10-year-old Arte, began to be consistently lame. MRI revealed a significant bone injury and ligament tears in his leg. PRP injections and other treatments had little effect so she consulted Peroni. “Dr. Peroni started talking to me about regenerative therapy and the stem cell,” she says. “So I said, ‘OK, let’s try it.’”

Peroni took stem cells from Arte’s bone marrow and grew them in the lab to get enough to make an impact. That process took two to three weeks and Delarios says Arte got two rounds of stem cell injections.

“I brought him home and kept him walking and moving around and gradually I was able to put him in light work,” she says. “And you know, he came back 100% jumping again so I was a big believer.

“Those ligament injuries are pretty bad,” she adds. “Tears or anything significant in the tendons can just be a death sentence.”

Equine insurance covered much of the costly treatments and Delarios says she recommends regenerative medicine to other horse owners. “When you invest in these animals, it’s a commitment and it’s your responsibility to take care of them and do whatever you can to preserve them because they are athletes, just like any other athlete.”

While Peroni is a proponent of regenerative medicine, he thinks the term conveys the wrong message to the public. “We just don’t regenerate new tissue in any shape or form,” he explains. “What these products are, are injury modulators. So in the veterinary world, we refer to them now more commonly as biological products, meaning derived from living cells or tissue or blood. What their ultimate goal is, is to modulate the healing response to end up with a better repaired tissue than would be there if you did not use them.” Again, helping the animal’s body repair itself and speeding up the healing process.

Buyer Beware

Peroni says the success of these treatments has led to a substantial downside – the rush to make money on unproven therapies for animals and humans, like claims that stem cells can be used to prevent or treat COVID-19 and macular degeneration. “Those financial gains have been commonly the motivating force behind putting products out that are supposed to be stem cells, and they have absolutely no science behind them,” he says. “They are poorly regulated, poorly studied and probably not particularly efficacious.”

He recommends pet owners ask the right questions to make sure they get scientific evidence about specific procedures.

“Stem cells don’t fall out of the sky,” he says. “It would be important to ask ‘where are the stem cells you’re going to put into my patient [coming] from?’ I would definitely ask ‘what is the science behind the choice and is there any evidence that the product is actually going to work?’”

His advice applies to human patients as well. Currently the only FDA-approved stem cell-based treatments for humans are those used to treat cancer and immune disorders. Often what’s advertised as an FDA-approved regenerative medicine treatment is actually something that complies with the agency’s rules for over 350 products that are not regulated as drugs. Practices and clinics abound selling unapproved stem cell therapies and scientifically unproven products, but the FDA does not have the resources to take action unless something poses a huge risk or causes an adverse reaction.

However, stem cell hype is attracting increased scrutiny. Last year, Georgia Attorney General Chris Carr filed a lawsuit against a healthcare company in Metro Atlanta for making false and misleading claims about the regenerative medicine products it offered. The suit alleges the company made more than $6.4 million through the use of aggressive marketing and high-pressure sales tactics to persuade more than 800 consumers – most of whom were disabled or elderly – to purchase unproven treatments not covered by health insurance or Medicare. The suit seeks consumer restitution and penalties of up to $10,000 for each violation of the Georgia Fair Business Practices Act.

“There are [physicians] in the community accepting $10,000 a year for stem cell injections when a joint replacement will cost $30,000 for the life of that joint replacement, and that’s 30 years,” says the Arthritis Foundation’s Kim. “I just encourage everybody to be thoughtful of getting something that has a lifetime of 30 years and comparing that to something like stem cell therapy that has insufficient data and costs so much money.” (A portion of joint replacement costs is covered by most insurance.)

The bottom line is that regenerative medicine has enormous potential, but most of it is still in the investigational stage so people must do their homework, ask questions and adjust their expectations.

“We’re really taking the lowest hanging fruit right now, and that’s the ability to do things like reduce inflammation and create an environment where the body can use its own system to repair it,” says Stice. “Understanding how the body forms cartilage or forms new nerve cells in the brain, those are the things that are in the future, and then making the body do that naturally through pushing the right buttons.”

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