Musculoskeletal conditions and the growth of regenerative medicine

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Musculoskeletal conditions and the growth of regenerative medicine

Dr Joshua Rothenberg, Director of Regenerative Medicine at BocaCare Orthopedics and Boca Raton Regional Hospital, discusses how blood products and biologic cellular components are being used to heal musculoskeletal conditions

​Throughout medicine, there are many advancements occurring, specifically in the field of orthopaedics. My subspecialty training, from the University of Pittsburgh Medical Center in sports medicine – with regenerative medicine as my particular focus – has allowed me to successfully treat patients in a more natural way over the last two years.

I was introduced to the field nearly five years ago by a leader in regenerative medicine, Dr Gerard Malanga, MD, which ultimately culminated in the advancement of my skills and knowledge under the direction of Jose Ramirez-Del Toro, MD, and Kentaro Onishi, DO at the University of Pittsburgh Medical Center.

Physicians, like me, and scientists across the globe are exploring the possibilities of using blood and cellular components to enhance tissue healing in both acute and chronic musculoskeletal conditions.

Clinically, we aim to reduce pain and improve function, and thus we are exploring more natural ways of doing so. Likewise, scientifically we want to be able to investigate the potential orthobiology may serve to aid in tissue healing and tissue enhancement for muscles, bones, cartilage, and tendon and ligament issues.

From tennis elbow (lateral epicondylosis) to osteoarthritis and other degenerative issues, regenerative medicine preliminarily appears to have had some successes for a variety of conditions. The treatments that we focus on are categorized as autologous, which is the use of blood or cellular components that come from the patient.

These autologous treatments are categorized as platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC) and microfragmented adipose therapies.

PRP has gained the most popularity recently, and is the most widely researched among these treatments. There are unconfirmed reports that it has been used to treat the injuries of well-known sports stars, including tennis player Rafael Nadal, golfer Tiger Woods and basketball players Stephen Curry and Kobe Bryant.

Platelet-rich plasma: how does it work?

Platelets are one of the first responders to an injury. For this reason, research has focused on platelets as possible tissue healers. They contain substances such as alpha and dense granules, important growth factors, and vasoactive proteins, which are believed to aid in enhancing the healing response.

PRP-based treatments involve the process of concentrating these platelets and suspending them in plasma, enabling the physician to deliver a greater amount of important growth factors, ultimately leading to tissue enhancement and greater blood flow to an injured area.

PRP dates back to the 1970s but its first documented use was in cardiac surgery in the late 1980s. It then took to the dental field, with its use increasing in the 1990s. It wasn’t until the early 2000s that PRP was used in the orthopaedic and musculoskeletal area. In 2006, Dr Allan Mishra, from the Department of Orthopedic Surgery at Stanford University Medical Center’s Menlo Medical Clinic published the first paper on treating tendinosis with PRP.

We believe that tissue enhancement using PRP may occur for injuries involving cartilage, tendons, ligaments, and muscles. Therefore, much of the research currently surrounds degenerative issues, such as osteoarthritis or chronic tendinosis. There is also relatively newer research that addresses disc issues in the spine.

We know that PRP is safe, and large well-controlled studies have demonstrated this. When compared to other types of injectables, preliminary research favors PRP’s safety profile and efficacy.

What’s more, PRP has also been used to enhance many surgical procedures, especially with healing and wound care. Its use therefore is not solely as a stand-alone treatment. Despite its apparent effectiveness, it is still not considered a first-line treatment, and there is no substitute for optimizing the body’s health through physical therapy, strengthening, and movement.

How cellular treatments promote tissue repair

BMAC and microfragmented adipose are cellular treatments that contain mesenchymal stem cells (MSCs), or what some believe are actually ‘signaling’ cells.

When there is tissue injury or damage, the body releases these cells to the site of injury. Although debate on exact mechanisms exists, recent research has focused on how these cells ‘home’ in on the site of injury, read the environment, signal the appropriate healing mediators and proteins for tissue repair and enhancement, and return to their origin. MSCs have migration, self-differentiation, and self-replication capabilities. They exhibit anti-inflammatory, anti-microbial, immune system regulation, anti-apoptotic (prevent cell death), cell-to-cell signaling, and paracrine/trophic effects. All of these are believed to contribute to tissue healing.

BMAC is an autologous biological treatment, in which cells from a patient’s bone marrow are collected from the pelvis. These are concentrated through centrifugation and injected into the area in need of treatment. Studies have shown that BMAC contains around 0.02% MSCs.

Large studies have determined bone marrow aspiration to be a relatively safe procedure. We are relatively young in our knowledge on this treatment clinically. In clinical studies, BMAC has often been demonstrated to decrease pain and stiffness, leading to functional improvement. The majority of studies are geared towards degenerative or cartilage-related injuries, such as osteoarthritis or cartilage defects.

Scientifically, in experimental models, MSCs have demonstrated an ability to reduce cartilage destruction, decrease subchondral (the layer of bone below the cartilage) remodeling and increase cartilage regeneration.

MSCs were first isolated in the 1970s, however our knowledge for musculoskeletal and orthopaedic issues is relatively new. Large studies are now under way looking at BMAC’s effectiveness throughout the body, with some early promising results. There is still much more work to be done, however.

In microfragmented adipose treatment, a patient’s adipose (fat) is harvested from the abdomen, buttocks, or flank (side of the body between the ribs and hip), washed of oils, processed via fragmenting (and in some cases centrifuging) and injected into the area in need of treatment, such as a degenerative joint or tendon tear. Adipose contains MSCs, which appear to be more numerous in number than those in BMAC. Studies have shown that adipose contains about 1-7% MSCs. It appears that adipose-derived MSCs behave in a similar manner to that of bone marrow-derived, exhibiting similar cell markers, along with migration, self-differentiation, and self-replication capabilities.

As with BMAC, our clinical and scientific literature needs to be more robust, and currently many clinical studies are underway to investigate the safety and effectiveness of microfragmented adipose treatment.

A close colleague and clinician-scientist, Dr Prathap Jayaram, MD, Director of Regenerative Medicine at Baylor College of Medicine, states “Our knowledge of bone marrow aspirate concentrate and microfragmented adipose is early in its orthopaedic applications. With a more mechanistic approach to regenerative medicine and scientific collaborations, we will be able to advance clinical outcomes.”

Global research and the need for consistent reporting

While there are many ongoing studies, our literature for PRP is far ahead that of adipose or BMAC. With PRP, however, we have inconsistent reporting standards that have caused confusion. Our most robust studies come from research into tennis elbow and knee osteoarthritis. We have seen defined improvement in pain and function for these areas with multiple randomized controlled trials.

Dr Malanga always stresses that we are in the third inning of a nine-inning baseball game with respect to our current knowledge of PRP, and not even at the national anthem for ‘stem cell’ treatments. We must work to standardize our classification so that our data is consistently compared. There are many ‘flavors’ of PRP, so having a standard way of reporting is necessary. Additionally, our physician community must critically evaluate both clinical and laboratory-based studies to determine the true effectiveness of these treatments.

Regenerative medicine: an exciting future ahead

Manufacturers and commercial devices have improved enough in recent years that we are largely able to isolate the blood components necessary to deliver a solid treatment. We want to individualize care because a ‘one size fits all’ model may not work for everyone.

There are active attempts to help quantify and qualify the treatments that are being delivered, and to improve our methods in order to deliver more individually tailored treatments.

My hope is that one day we will have enough literature and systems in place to ‘dose’ these products for tendons, cartilage, ligaments, and muscles. I believe we will have the ability at bedside to understand the exact number of blood components or cellular components that are needed for the pathology that needs to be treated, and we will be able to give appropriate rehabilitation to heal these injured areas.

Lastly, we now know in order to deliver an optimal treatment, that imaging guidance serves an important role. Another technological advancement in orthopaedics, musculoskeletal ultrasound, is paramount to delivering these biologic products with precision and accuracy to the areas of pathology. This gives our treatments the greatest ability to be effective.

Remember, the ultimate goal is to diminish pain and improve function while stimulating healing.

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