Regenerative Medicine: Helping the Body Heal Itself
No longer the stuff of science fiction, regenerative medicine is the future of health care.
By Linda Rath | Updated Aug. 10, 2023
The body is astonishingly good at healing itself. It mends broken bones, seals cuts and bounces back from the flu. But if it’s overwhelmed by injury or illness, then regenerative medicine may be a solution. Using breakthroughs in cell therapy, bioengineering and gene therapy, regenerative medicine aims to stimulate and support the body’s natural healing response. Regenerative therapies are considered the future of medicine and represent a seismic shift away from traditional medical treatment. They show promise for osteoarthritis (OA) and many other chronic diseases that have no cure, including diabetes, cancer and neurodegenerative disorders like Parkinson’s disease.
The regenerative medicine field is changing rapidly. Therapies like microfracture, once used to treat cartilage defects in the knee that could lead to arthritis, have largely been abandoned in the U.S. Meanwhile, new treatments are in various stages of research or clinical trials. Ideas about some of the more provocative aspects of regenerative medicine, such as stem cells, are also changing, although they still stir controversy and debate.
Here’s a rundown of some current and potential regenerative treatments. Although some are not FDA-approved for arthritis, many are used to treat patients at academic medical centers across the country.
Platelet-rich plasma (PRP)
PRP got a lot of press in the early 2000s, when top athletes started using it to recover from slow-healing injuries. Since then, doctors have successfully used it to treat everything from OA pain, especially in the knees, hips and shoulders, to damaged tendons, hair loss and aging skin.
The process is simple. A person’s blood is drawn and spun in a centrifuge. This separates out the platelets and concentrates them in plasma, the liquid part of blood. The platelet-rich plasma is then injected into tissue damaged by injury, aging or disease. The platelets themselves don’t stick around for long, but the growth factors, anti-inflammatory proteins and signaling molecules they produce can boost healing, regulate immune cell function and improve symptoms.
Scott Rodeo, an orthopedic surgeon and director of the Center for Regenerative Medicine at Hospital for Special Surgery in New York City, has studied PRP extensively and uses it to treat OA pain in some patients.
“There is robust data that it is helpful for symptom improvement, and because it lasts six months or more, it’s more durable than [corticosteroid or hyaluronic acid] injections. PRP is made from a person’s own blood, so it’s very safe.”
- The makeup and potency of PRP can vary, depending on the preparation method, type of centrifuge, time of day, even what a patient ate. That’s one reason studies of PRP often have conflicting results. “PRP that works for arthritis may not work for tendinosis,” Dr. Rodeo says. “We need to learn how to tailor it to a particular type of tissue as well as a person’s age, gender and comorbidities.”
- Evidence suggests blood products like PRP are symptom-modifying but not structure-modifying. This means they relieve symptoms but may not regenerate tissue.
- PRP isn’t covered by insurance. In 2019, out-of-pocket costs for PRP averaged about $1,000 per injected area.
Stem cells have generated enormous interest among researchers and the public. That’s because some stem cells can turn into many different types of cells and have great potential to repair or replace damaged or aging tissue. Research institutions in nearly every country are conducting clinical trials using stem cells to treat a vast array of conditions. At least half the clinical trials in Mayo Clinic’s Center for Regenerative Biotherapeutics involve stem cells.
The key words are clinical trials. The FDA has approved stem cells for treating certain cancers and disorders of the blood and immune system. But it warns consumers about unproven and likely ineffective stem cell therapies offered at the nation’s nearly 3,000 for-profit stem cell clinics. You can read the Arthritis Foundation’s statement about these clinics here.
You will be hearing more and more about stem cells. Here’s the current rundown:
- Embryonic stem cells. These cells are pluripotent, meaning they can turn into any of the 200 cell types in the body. But they only exist in the first three to five days of embryonic development. According to Irving Weissman, a stem cell pioneer and emeritus director of Stanford University’s Institute of Stem Cell Biology and Regenerative Medicine, embryonic stem cells are every part of the body packed into one small blastocyte. After a few days, the cells have already started to differentiate into specialized tissues like the lungs, intestine and brain. Embryonic stem cells have great promise for tissue repair and regeneration but have long been plagued by ethical and political controversies.
- Adult stem cells. These are found in small numbers in many organs and tissues in the body, especially bone marrow and fat. Adult stem cells can replace themselves when they’re damaged by injury or disease, though this lessens with age. Scientists used to think adult stem cells could only create similar cells, but it’s now known they have some ability to turn into other cell types. Adult stem cells also interact with the immune system, creating a microenvironment that may boost tissue regeneration. Mayo Clinic researchers are conducting clinical trials using stem cells from both fat and bone marrow to treat OA as well as heart failure and neurological diseases. More recently, researchers at Stanford University were able to regrow cartilage in mice as well as human tissue by guiding skeletal stem cells to produce cartilage instead of bone. Cartilage, which cushions the ends of bones in joints, can’t regrow on its own and contains no stem cells, so this could be a potential breakthrough for people with OA. The researchers say it might also be used as a routine tune-up to maintain cartilage health. (The Stanford research was partially supported by the Arthritis Foundation).
- Induced pluripotent stem cells (iPSCs). Hailed as a breakthrough in stem cell technology, iPSCs are the Nobel Prize-winning discovery of Japanese researcher Shinya Yamanaka. He found that adult stem cells from almost any part of the body could be genetically reprogrammed back to an embryonic state. This would avoid ethical concerns about embryonic stem cells while guaranteeing an almost unlimited supply of individualized pluripotent cells. But iPSCs are still in preclinical trials amid concerns about their safety and the tedious reprogramming process.
- Very small embryonic-like stem cells (VSELs). These tiny, potentially pluripotent cells are the UFOs of stem cells. There is no evidence they exist, but some researchers claim to have seen them in certain adult tissues.
Autologous microfragmented adipose tissue (AMAT or MFAT)
Think of this as fat-based PRP. A small amount of fat is removed from a patient’s belly via liposuction – a minimally invasive procedure. The fat is washed and chopped into small pieces (microfragmented) in a special device, then injected into the area needing treatment. Fat contains stem cells as well as pericytes, vascular cells that act much like adult stem cells. Although AMAT is sometimes used to treat a variety of problems, such as tendon and meniscus tears, back pain and rotator cuff injuries, many studies have focused on OA. Researchers in academic medical centers have shown that microfragmented fat can significantly improve OA pain and function, regardless of a patient’s age, weight or stage of arthritis. In one small head-to-head comparison with PRP plus hyaluronic acid, both treatments led to similar improvements in knee pain, function and quality of life.
Keep in mind:
- The quality of AMAT can vary, depending on how the fat is collected and the type of device used to purify it.
- Experts say the protocols for PRP have been refined and standardized, leading to more consistent results. But that may not hold true for AMAT and bone marrow aspirate, which uses the liquid part of a patient’s bone marrow to reduce inflammation and repair joints and tendons. “We need more data,” Dr. Rodeo says. “We need to characterize what we’re putting into patients; [right now], we have no idea.”
Repairing and regenerating cartilage with tissue
Before the 1990s, there were few ways to surgically repair worn or damaged cartilage in the joints. Now, there are several options. Some use a patient’s own (autologous) tissue; others use donor (allogeneic) or lab-made tissue. These procedures treat small, localized areas of cartilage damage, not arthritis itself. The goal is to prevent progressive changes that lead to arthritis. These are approved treatments covered by insurance:
- Osteochondral autograft transplantation surgery (OATS). Surgeons take articular cartilage from a healthy part of the knee that doesn’t bear weight and use it to repair a small area of damaged knee cartilage. OATS is used for small to moderate lesions because, Dr. Rodeo says, “You can only take so much healthy cartilage.” Autografts, using a patient’s own tissue, are more predictable and long-lasting than allografts, which use donor tissue to target larger lesions.
- Matrix-induced autologous chondrocyte implantation (MACI). This is one of the most common techniques for repairing knee cartilage, with an 80% to 90% success rate over time. In a two-step procedure, surgeons remove a small sample of healthy knee tissue. The cells are grown in a lab on a collagen matrix or scaffold for about a month. When ready, the implant is trimmed to fit the cartilage defect and secured in place with fibrin glue. In time, the implant integrates with existing cartilage. Next-generation MACI, still in the experimental stage, uses 3D printing for cartilage and bone reconstruction. At Mayo Clinic, researchers are studying the safety and effectiveness of a single-step cartilage repair process that combines a patient’s own cartilage cells with donor stem cells (RECLAIM).
Works in progress
Regenerative medicine is rapidly expanding to include gene editing and gene therapies. Farshid Guilak, PhD, co-director of the Washington University School of Medicine’s Center of Regenerative Medicine, in St. Louis, is using the gene-editing tool CRISPR-Cas9 to create custom-designed cells and drug screening for OA.
In the Musculoskeletal Gene Therapy Research Laboratory at Mayo Clinic in Minnesota, principal investigator Christopher Evans, PhD, is leading a clinical trial to test the safety of a gene therapy called sc-rAAV2.5IL-1Ra, which is carried by a virus and injected into arthritic knees.
Both Guilak’s and Evans’ work is based on research that highlights the role of inflammatory proteins in OA, especially interleukin-1 (IL-1). IL-1Ra naturally inhibits this protein. Guilak has used CRISPR to edit out the IL-1 signaling pathway in mice, while Evans uses a gene transfer technique to deliver IL-1Ra to human joints.
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