Orthobiologics: A New Frontier for Musculoskeletal Disease

Keywords

Orthobiologics; PRP; BMC; Adipose-derived Stem Cells; Umbilical Cord-derived Cells

The past 20 years of medicine has seen an unprecedented rate of scientific discovery, providing a greater understanding of disease pathology and processes, eliciting a new area of medicine called “Orthobiologics”. Orthobiologics have a specific emphasis on tissue healing and biological restoration by harnessing the regenerative potential within the body’s own cells and redirecting their use for accelerated healing in damaged or diseased tissues. In the field of Sports Medicine, Orthobiologics have prompted a paradigm shift in treatment; from temporary symptomatic management to delay or disease prevention by modifying cell signals within the biologic environment. Many cellular therapies are evolving as a bridge between conservative non-invasive options and invasive surgical treatments. Thus far, Orthobiologics have experienced three generations of evolution, beginning with visco supplementation, or Hyaluronic Acid, progressing to Platelet Rich Plasma [1] and Bone Marrow Concentrate. Recent reports of Adipose and Umbilical Cord Derived Cells and specific growth factors such as BMP 7 [2] are now also found in the literature.

First generation Orthobiologics were available in the clinic in 1997 and consisted solely of Hyaluronic Acid (HA), a viscosupplementation for joint arthritis. HA reduced painful symptoms of osteoarthritis in those patients who responded to treatment and provided a superior safety profile when compared to continuous NSAID use for pain control [3-5].

Platelet Rich Plasma (PRP) didn’t appear in the sports medicine literature until 2006; however, this 2nd generation of Orthobiologics was actually first used by Ferrari et al in 1987 following open heart surgery [6]. PRP was the first autologous Orthobiologic and used previously in many therapeutic areas including ENT, maxillofacial surgery, ophthalmology, urology, dentistry, cosmetic and neurosurgery as well as wound healing. Scientists studying wound healing discovered that platelets were not solely involved in clotting, but that they contained several bioactive proteins, such as stromal-derived factor 1a, as well as growth factors like TGFb-1, IGF-1, bFGF, BMP-2, etc., which encourage regenerative potential and healing properties [7,8]. Theoretically, the potent concentration of platelets are administered to stimulate a supra-physiologic response, as they are comprised of an undifferentiated cocktail of anti-inflammatory, pro-inflammatory, anabolic, and catabolic mediators in an attempt to elicit the body’s natural healing response. Although, most of the literature consists of small case series [9,10], larger randomized controlled trials have demonstrated superior efficacy in areas such as tendinopathies [11,12] and knee osteoarthritis [13-16]. The authors recently published results of a multicenter, blinded controlled trial on leukocyte rich PRP use for lateral epicondylitis. Success rates for patients at 24 weeks post-treatment were 83.9% in the PRP group compared with 68.3% in the control group (P = .037) [11]. More recently, biologic injections have been applied to the spine. Prospective double blind randomized controlled data from the Hospital of Special Surgery (HSS) demonstrated improved outcomes with intra-discal PRP [17]. PRP injections for facet mediated joint pain have previously been described although warrants further clinical trials [18]. PRP applications will continue to expand with the growing volume of literature and mainstream publicity from PRP use in professional athletes; albeit, consistent guidelines for the variety of applications remain lacking. Standardization for optimal outcomes is needed to clarify which PRP preparation and protocol variables are best for which musculoskeletal conditions.

Bone Marrow Concentrate (BMC) is considered the 3rd generation of Orthobiologic therapy. See Figure 1. It has a potent mixture of mesenchymal stem cells (MSCs), hematopoetic cells, platelets, and cytokines noted for possessing anti-inflammatory, immunomodulatory, and chondrogenic properties, which act as the foundation for its regenerative potential [19]. Although the exact mechanism is unknown, it is hypothesized that the bone marrow concentrate mileau either induces differentiation and proliferation of resident stem cells, or possesses innate chondrogenic potential [19]. Dr. Caplan recently lectured at the 2014 (TOBI) The Orthobiologic Institute regenerative medicine symposium, suggesting that perivascular cells or Pericytes, adhere to blood vessels and act as one of our body’s largest reservoirs for Mesenchymal Stem Cells. He explained that when the body undergoes trauma, soluble factors within the perivascular space cause the release of Pericytes from microvessels. Pericytes act as “Medicinal Signaling Cells” once released, where they can be activated into Mesenchymal Stem Cells, exhibiting trophic, immunomodulatory, and osteogenic roles. Dr. Caplan’s research continues to expand our understanding of MSCs and provides insight into the potential therapeutic mechanisms of Mesenchymal Stem Cells [20].

Figure 1:  Harvesting of Bone Marrow Concentrate (BMC).