Platelet-Rich Plasma Effects on Degenerative Disk Disease: Analysis of Histology and Imaging in an Animal Model

Abstract

Introduction The current conservative and surgical modalities of treating degenerative disk disease are aimed at relief of symptoms. At this time, there is no cure for the degenerative process. Platelet-rich plasma (PRP) is a bioactive component of autologous whole blood. The indications for the use of PRP in the treatment of musculoskeletal diseases continue to expand. The mechanism of action for PRP is due to the release of healing factors from platelets. While clinical evidence strongly supports the use of PRP for certain conditions, the potential benefit of PRP in treating or preventing progression of degenerative disk disease has not been critically evaluated. There is a preliminary evidence that certain growth factors in PRP, such as PDGF and IGF-1, may be beneficial in slowing the progression of disease. The objective of this study is to analyze the early and late phase effects of PRP injection into the intervertebral disk using an animal model. Materials and Methods After obtaining IRB and Institutional Animal Care and Use Committee (IACUC) approval, the L4-L5 intervertebral disk of adult Sprague Dawley rats were injured with a 21-gauge needle in 24 rats. After injury, animals received either an acute injection of PRP collected from matched donor animals, a delayed (2 week) injection of PRP after the degenerative process had commenced, or no further intervention (sham PRP). Magnetic resonance imaging was performed for each group at 0, 2, and 4 weeks. Three rats were euthanized at 2 weeks post-PRP injection, as well as three shams and a control rat. We collected traumatized and adjacent discs in test subjects, along with discs from control subjects. Each disk was sectioned axially and sagittally followed by histopathological and immunohistochemical analysis. Results The disks treated with PRP, both in the acute and delayed administration, had less degeneration than the sham group. The sham group had clear degenerative changes with near total loss of organizational structure, large amounts of empty space, fibrous (scar) tissue, and large numbers of inflammatory cells (Fig. 2). The PRP-treated group had annulus fibers that were damaged with some empty spaces and inflammatory cells. However, there was a maintenance of the ring structure and the nucleus pulposus, while having irregular borders and overall deceased size, appeared to have a healthy central portion (Fig. 3). Overall, the PRP treated group retained more normal morphologic features of the control disks (Fig. 1), contained fewer inflammatory cells than those not receiving PRP, and did not appear as damaged on MRI. The disk height did not seem to be greatly different between all three groups at the 2 weeks interval. Conclusion The needle puncture technique was validated as an effective method for creating a degenerative disk model. The administration of PRP has a protective effect on damaged disks and decreases the amount of inflammation at the 2-week interval and the 6-week interval. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest R. Mcguire Grant/Research support from: spinal usa, stryker, Consultant for: synthes Chen WH, Liu HY, Lo WC, et al. Intervertebral disk regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. Biomaterials 2009;29:5523–33. Epub 2009 Jul 30 Sawamura K, Ikeda T, Nagae M, et al. Characterization of in vivo effects of platelet-rich plasma and biodegradable gelatin hydrogel microspheres on degenerated intervertebral discs. Tissue Engineering Part A 2009;12:3719–3727 Nagae M, Ikeda T, Mikami Y, et al. Intervertebral disk regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. Tissue Engineering 2007;1:147–158 Akeda K, An HS, Pichika R, et al. Platelet-rich plasma (PRP) stimulates the extracellular matrix metabolism of porcine nucleus pulposus and anulus fibrosus cells cultured in alginate beads. Spine 2006;31(9):959–966 Chen WH, Lo WC, Lee JJ, et al. Tissue-engineered intervertebral disk and chondrogenesis using human nucleus pulposus regulated through TGF-beta1 in platelet-rich plasma. Journal of Cellular Physiology 2006;209(3):744–754 Elliot DM, Yerramalli CS, Beckstein JC, Boxberger JI, Johannessen W, Vresilovic EJ. The effect of relative needle diameter in puncture and sham injection animal models of degeneration. Spine 2008;33(6):588–596