Regenerative Medicine
Prathap Jayaram, MD
Joslyn John, MD
Nicolas Karvelas, MD
FAST FACTS
Platelet rich plasma (PRP) and mesenchymal stem cell (MSC) therapy are regenerative strategies for musculoskeletal injuries.
Osteoarthritis and tendinopathy are disease processes in which regenerative strategies have demonstrated clinical value.
Although regenerative strategies are showing promise, they should be used in conjunction with rather than replace standard treatments, including prescriptive physical therapy, adaptive equipment, and bracing.
REGENERATIVE STRATEGIES FOR MUSCULOSKELETAL INJURIES
Introduction to Regenerative Medicine
Regenerative medicine has gained increased popularity in modern medical delivery strategies. At its core, regenerative medicine aims to restore diseased tissue to a healthier physiologic baseline. In the last decade there has been an explosive application of regenerative strategies for musculoskeletal pathology. The recent literature has demonstrated certain regenerative strategies to have excellent safety profile with improved clinical outcomes in musculoskeletal injuries.1 Osteoarthritis (OA) and tendinopathy are 2 particular disease processes that commonly present to the primary care physician and in which regenerative strategies have shown clinical value. This chapter focuses on clinical applications of platelet rich plasma (PRP) and mesenchymal stem cell (MSC) therapy as it pertains to the primary care physician. While stem cell products in orthopedic applications have the potential to treat many medical conditions, it is not fully known if such products have clear benefit or if the products are entirely safe to use at this time. Seek information directly from the Food and Drug Administration for current guidelines and the status of stem cell therapies under investigation. Also seek information from Academic Physicians who specialize in the field or are involved in Clinical Stem Cell Research.
Definition and Mechanism of Action
Platelet Rich Plasma
PRP by definition is inherently an autologous derivative blood product with a higher physiologic concentration of platelets.2 Although PRP has been used more routinely in clinical practice, its exact mechanism in the reparative spectrum is still being explored. The common theory is that platelets house certain growth factors through its alpha granules and once degranulated are able to alter the microenvironment allowing for optimization of tissues with, otherwise, low intrinsic healing potential.1 Specific applications and evidence of PRP will be explained in tendinopathy and osteoarthritis sections.
Mesenchymal Stem Cells
Adult MSCs are found abundantly in many tissue constructs. For orthopedic applications, adipose and bone marrow-derived MSCs have been much of the clinical
focus. Adults MSCs are derived from perivascular cells, pericytes.3 Once a pericyte has been dissociated from its native blood vessel and exposed to the surrounding environment, it becomes an MSC proper.3 MSCs have multiple mechanisms that include anti-inflammatory, immunomodulatory, and paracrine effects.1 Much like PRP the exact mechanism of MSC-derived therapy is still being explored and still in its infancy in terms of delineating exact mechanisms. The following text explains specific applications and evidence of MSC-derived therapy.
focus. Adults MSCs are derived from perivascular cells, pericytes.3 Once a pericyte has been dissociated from its native blood vessel and exposed to the surrounding environment, it becomes an MSC proper.3 MSCs have multiple mechanisms that include anti-inflammatory, immunomodulatory, and paracrine effects.1 Much like PRP the exact mechanism of MSC-derived therapy is still being explored and still in its infancy in terms of delineating exact mechanisms. The following text explains specific applications and evidence of MSC-derived therapy.
Common Conditions Presenting to Primary Care: Tendinopathy/Osteoarthritis and Supporting Evidence
Tendinopathy
Tendinopathy and OA are some of the more prevalent diagnoses that present to the primary care physician. Tendinopathy, a common degenerative condition, is thought to arise from a disordered healing response to an acute inflammatory episode within a tendon.4 This initial insult is repeated chronically through tendon overload resulting in microscopic alterations at the cellular level that weaken mechanical properties of the tendon.4 The more common anatomic presentations of tendinopathy are located in the lateral elbow (wrist extensor tendinopathy), shoulder (rotator cuff tendinopathy), hip (gluteal tendinopathy), knee (patellar tendinopathy), and ankle (Achilles tendinopathy). Rotator cuff tendinopathy accounts for 30% of shoulder-related pain,5 and gluteal tendinopathy is the most common in the lower extremity tendinopathy, attributing to a large percentage of hip-related pathology.6
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