The Future of Joint Repair (2022)

The science of regenerative medicine has not caught up with the hype, but shows potential for pain relief.

Regenerative medicine is an umbrella term for a branch of medicine that uses stem cells and tissueengineering to “fix” tissues that have failed to repair themselves. 

But expectations for regenerative medicine have sometimes gotten ahead of the science. Although its potential to repair and rebuildcartilagehas not been fulfilled yet, it has had successes, especially for pain relief.

This boomingfieldhas been largely unregulated. So it’s important to separate what goes on in reputable research institutions from certain for-profit clinics that hawk therapies of questionable value.

Regenerative medicine – which is being tried primarily in osteoarthritis (OA) --has two branches. One is tissue engineering, whichtriesto createreplacements for damaged tissue. The other is self-healing,which usesinjections of stemcells orblood productsto push thebodyto repair itself. 

Platelet Rich Plasma

Platelet-rich plasma (PRP) is probably most widely performedof theseprocedures. Blood is drawn from the patient and spun in a centrifuge to separate the platelets from other blood components. The platelets are then injected into problem areas.

How it Works:Yourbody’s first responseto injuryis to send plateletsto the site. This blood componentcontainsgrowth factors and other nutrients.PRP is thought to boost that natural response.

Benefits:PRP is done fairly quickly and generally requires only one injection.It providessymptomatic reliefthat may last three to six months.In some studies, PRP outperformed and sometimes outlasted hyaluronic acid or corticosteroid injections.“But does it have a benefit that goes beyond pain relief? We just don’t know,”saysChristopher Evans, PhD,director ofMayo Clinic’s Musculoskeletal Gene Therapy Research Lab.

Keep in mind:Studies suggest the preparation method, the type of centrifuge used and even the delivery method can significantly affect the results.Most insurers don’t cover PRP;out-of-pocket costs can range from $500 to $2,000.

Autologous Conditioned Serum

Called Orthokine in Europe andRegenokine in the United States, ACS usesthe patient’s own blood to fight pain. Your bloodis processed to increase the anti-inflammatory proteinsand growth factors it contains. Then it is injected in your affected joints,usually in a series of shots.

How it works:Regenokine blocks interleukin-1 (IL-1), a key player in inflammation. Itrelieves pain andcould conceivably slowOAdamage.

Benefits:Dr. Evans says the treatment is safe and well-tolerated.Like PRP, studies show only symptom relief, but no evidence of any tissue regrowth.

Keep in mind:ACS is more commonly used for muscle, tendon and ligament damage than it is for arthritis.Itis more complex and less readily available than PRP and the cost may be as high as $10,000 a session.

Stem Cells

Stem cells can make copies of themselves andturn into other types of cells. In adults, a small number of these unspecialized cells lie dormant in many organs and tissues. The idea that stemcells might be a source of renewable tissue for almost any part of the bodyis the basis for this line of treatments.

How it works:Mesenchymal stem cells (MSCs),which arefound mainly in bone marrow and fat, are usually used for these procedures.Thestemcells areseparatedfrom other tissuecomponents and arethen injected into your painful joint. The theory is that the stem cells will initiate tissue regeneration in the joint.

Benefits:MSCs stimulate the production ofanti-inflammatory proteins and growth factors.There is evidence – from studies of varying quality – that MSCs are safe and can improve pain and function in arthritic joints.

Riley Williams III, MD, who directs the Institute for Cartilage Repair at the Hospital for Special Surgery (HSS) in New York Citysays,“I’m really excited about the prospects for treating very early arthritis and some chronic overuse injuries. [Stem cells] are not going to work for bone-on-bone arthritis, but they are helpful when people are just starting to have some pain and swelling.”

Keep in mind:There’s no evidence that stem cells can restore lost tissue or cause cartilage to grow.

“The number of true stem cells in bone marrow and fat is vanishingly small,” explains Brian Halpern, MD, a sports medicine specialist at HSS. “If we could take the bone marrow to the lab and isolate the small population of stem cells and expand them in culture – then we’d really have something,” he says. But the FDA prohibits that in the USat this time.It’s done in much of the rest of the world,however.

Most insurers won’t pay for stem cell therapies.Theprice of a single knee injection at direct-to-consumer stem cell clinics is around $5,100.

Cartilage Repair and Restoration

When smallholesor tears develop in cartilage, usually as a result of injury, they can leave areas of bare bone. Over time, these can lead to OA. Filling them with repair tissue can relieve pain, improve function and delay or prevent the need for surgery later on.A few different techniques are available.

How it works:Microfracture involves drilling tiny holes in the bony layer under the defect, where a blood clot forms and eventually fibrocartilagegrows. Fibrocartilageisn’t as strong or durable as the cartilage we were born with (called hyaline cartilage).

In cartilage transplantation, aplug of cartilage and bone istakeneither froma healthy part ofyourkneeor from a donated source at a tissue bank. The plug is thentransplantedintothecartilagedefect.

Matrix-associated autologous chondrocyte implantation (MACI) involves removinga small piece of cartilage from a non-weight-bearing part of the knee. It’s sent to a lab where the cartilage cells are grown on a membrane.The resultingmembranesheetcan be cut to fit the defect.Two similar procedures – NeoCart and Novocart 3D – are in clinical trials and likely to be approved within the next few years.

Benefits:Most cartilage transplantsare successful, and 88 percentof patientsreturn to sport.Allograft and autograft transplants are becoming primary treatment strategies, particularly for younger athletes and active people.

Studies show that about 85 percent of MACIimplants survive and integratewith existing cartilage.

Keep in mind:None of these cartilage restoration techniques areintended for people with widespread damage from arthritis.

In-network cost for a single-knee allograft is about $14,000 and autografts are about $11,000.Current pharmacy pricesfor MACIare around $40,000; the other two will be priced after they receive FDA approval.

Works in Progress

Stem cells wrapped in cartilage:Jeffrey Lotz, PhD, director of the Orthopaedic Bioengineering Laboratory at the University of California, San Francisco, wrapped MSCs in a sheath of cartilage cells that signal the MSCs to become cartilage. It’s worked in animal models of arthritis; whether it will work in other larger animal models and humans remains to be seen.

Hydrogel scaffolds:Jennifer Elisseeff, PhD, director of the Translational Tissue Engineering Program at Johns HopkinsUniversityinvented a scaffold to help repair cartilage defects. The gel starts out soft, smooth and watery, and cartilage cells grow in it. In a small clinical trial, the gel, injected into a defect after microfracture, significantly improved results of the procedure. Patients formed less scar tissue and more “normal” cartilage.Elisseeff also invented anadhesive that bonds to the hydrogel and cartilage,whichhelpsnew cells to integrate with existing tissue.

Anti-inflammatory solutions:Farshid Guilak, PhD, co-director of the Washington University Center of Regenerative Medicine in St. Louis, Missouri (and an Arthritis Foundation-funded researcher), is working on anti-inflammatory solutions that include purified stem cell injections and a combination of gene therapy and tissue engineering to improve the body’s repair mechanisms.

Sources

Sources

Baltzer AW, et al. Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis.
https://www.ncbi.nlm.nih.gov/pubmed/18674932

DeCaro F, et al. Large fresh osteochondral allografts of the knee: a systematic clinical and basic science review of the literature.
https://www.ncbi.nlm.nih.gov/pubmed/25660010

García-Escudero JB and Hernández Trillos PM. Treatment of Osteoarthritis of the Knee with a Combination of Autologous Conditioned Serum and Physiotherapy: A Two-Year Observational Study.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692499/

Gracitelli GC, et al. Fresh osteochondral allografts in the knee: comparison of primary transplantation versus transplantation after failure of previous subchondral marrow stimulation.
https://www.ncbi.nlm.nih.gov/pubmed/25817190

Kreuz PC, et al. Platelet-Rich Plasma Preparation Types Show Impact on Chondrogenic Differentiation, Migration, and Proliferation of Human Subchondral Mesenchymal Progenitor Cells.
https://www.ncbi.nlm.nih.gov/pubmed/25980401

National Institutes of Health. Stem Cell Information.
https://stemcells.nih.gov/research/international.htm

Piuzzi NS, et al. The Stem-Cell Market for the Treatment of Knee Osteoarthritis: A Patient Perspective.
https://www.thieme-connect.de/DOI/DOI?10.1055/s-0037-1604443

Ratcliffe E, et al. Current status and perspectives on stem cell-based therapies undergoing clinical trials for regenerative medicine: case studies.
https://academic.oup.com/bmb/article/108/1/73/347432

Suzuki K, et a l. Enhancement of Anti-Inflammatory and Osteogenic Abilities of Mesenchymal Stem Cells via Cell-to-Cell Adhesion to Periodontal Ligament-Derived Fibroblasts.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266859/

Vega A, et al. Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial.
https://insights.ovid.com/crossref?an=00007890-201508000-00027

Yubo M, et al. Clinical efficacy and safety of mesenchymal stem cell transplantation for osteoarthritis treatment: A meta-analysis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407776/

Personal Communications:

Jennifer Elisseeff, PhD, Cell and Tissue Engineering Program, Johns Hopkins University

Christopher Evans, PhD, Musculoskeletal Gene Therapy Research, Mayo Clinic

Farshid Guilak, PhD, Washington University Medical Center in St. Louis

Brian Halpern, MD, Hospital for Special Surgery

Wellington Hsu, MD, Northwestern University Feinberg School of Medicine

Jeffrey Lotz, PhD, Orthopaedic Bioengineering Laboratory, University of California, San Francisco

Nicolas Piuzzi, MD, Cleveland Clinic

Riley Williams, III, MD, Institute for Cartilage Repair, Hospital for Special Surgery

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