Clinical evaluation of autologous platelet-rich plasma for the treatment of tendinous and ligamentous lesions in 7 horses

Injuries of tendons and ligaments heal slowly and inefficiently. Once a lesion is produced, these structures do not recover their original biomechanical properties. It has been hypothesized that factors like fatigue, hypoxemia, hyperthermia, and overstrain can unchain a degenerative process of the extracellular matrix (ECM) of these tissues (17), including changes in the collagen molecules ratio with a shift to collagen type III (Col-III) production in detriment of Col-I synthesis (11), and death of resident cells (20). However, the exact pathophysiologic mechanism that produces these changes remains not well understood (13, 27).

The presence of catabolic cytokines, such as tumor necrosis factor alpha  and interleukin 1 alpha and beta in biopsies of equine tendons suffering from chronic tendinopathy has been reported (18). It has been shown that the exogenous administration of IL-1 to human tenocytes upregulates the expression of IL-1 and IL-6, cyclo-oxigenase 2 (COX-2), and matrix metalloproteinases (MMPs). It is known that all these substances have catabolic and inflammatory properties which have detrimental effects on ECM and resident cells of many tissues, including tendons and ligaments (32).

The negative effects of IL-1 or TNF- on connective tissue could be downregulated by some growth factors (GFs) (33). Studies in vitro have demonstrated the beneficial properties of transforming growth factor beta (2, 23, 24,), insulin like growth factor I (IGF-I) (9), vascular endothelial growth factor (VEGF) (35), fibroblastic growth factor (FGF)(23, 34), epidermal growth factor (EGF) and 6 platelet derived growth factor (PDGF) (23, 34) on tendon and ligament metabolism of different animal species. Moreover, Dahlgren et al (10) described a positive action of IGF-I in a collagenase induced tendonitis model of the equine superficial digital flexor tendon (SDFT). The results from these studies suggest the possible benefit of using GFs as a complementary treatment of soft tissue musculoskeletal injuries, either using pure recombinant proteins or gene therapy (6, 9, 12).

Platelet-rich plasma (PRP) is a natural and autologous source of some GFs, especially TGF-1, TGF-2, PDGF, VEGF, EGF, FGF and of other molecules that modulate inflammation and the tissue repair process (2, 3, 30). Platelet rich plasma has been used successfully in human medicine, for several purposes, including alveolar-maxilar reconstruction (2, 7), plastic (5), and orthopedic surgery (2). Moreover, there are anecdotic reports about the use of PRP for the treatment of Achilles tendonitis in two athletes and for cartilaginous avulsion in a football player (26). Recently, Anitua et al (3) documented the positive effects of PRP on human tenocytes. In that study, PRP produced tenocyte proliferation and upregulation of two angiogenic peptides, VEGF and hepatocyte growth factor (HGF).