Shawn Robert Browning

Platelet-rich plasma increases matrix metalloproteinases in cultures of human synovial fibroblasts.

BACKGROUND The effect of platelet-rich plasma on chondrocytes has been studied in cell and tissue culture. Less attention has been given to the effect of platelet-rich plasma on nonchondrocytic cell lineages within synovial joints, such as fibroblast-like synoviocytes, which produce cytokines and matrix metalloproteinases (MMPs) that mediate cartilage catabolism. The purpose of the present study was to determine the effect of platelet-rich plasma on cytokines and proteases produced by fibroblast-like synoviocytes. METHODS Platelet-rich plasma and platelet-poor plasma from harvested autologous blood were prepared with a commercially available system. Fibroblast-like synoviocytes were treated with platelet-rich plasma, platelet-poor plasma, recombinant PDGFββ (platelet-derived growth factor ββ), or phosphate-buffered saline solution and incubated at 37°C for forty-eight hours. The concentrations of IL-1β (interleukin-1β), IL-1RA (IL-1 receptor antagonist), IL-6, IFN-γ (interferon-γ), IP-10 (interferon gamma-induced protein 10), MCP-1 (monocyte chemotactic protein-1), MIP-1β (macrophage inflammatory protein-1β), PDGFββ, RANTES, TNF-α (tumor necrosis factor-α), VEGF (vascular endothelial growth factor), MMP-1, MMP-3, and MMP-9 in the culture medium were determined by multiplex immunoassay. RESULTS Platelet-rich plasma cultured in medium contained multiple catabolic mediators in substantial concentrations, including MMP-9 (15.8 ± 2.3 ng/mL) and MMP-1 (2.5 ± 0.8 ng/mL), as well as proinflammatory mediators IL-1β, IL-6, IFN-γ, IP-10, MCP-1, MIP-1β, RANTES, and TNF-α in concentrations between 20 pg/mL and 20 ng/mL. Platelet-poor plasma contained significantly lower concentrations of these compounds. Platelet-rich plasma was used to treat human fibroblast-like synoviocytes, and the resulting concentrations of mediators were corrected for the concentrations in the platelet-rich plasma alone. Compared with untreated fibroblast-like synoviocytes, synoviocytes treated with platelet-rich plasma exhibited significantly greater levels of MMP-1 (363 ± 94.0 ng/mL, p = 0.018) and MMP-3 (278 ± 90.0 ng/mL, p = 0.018). In contrast, platelet-poor plasma had little effect on mediators secreted by the synoviocytes. PDGFββ-treated fibroblast-like synoviocytes exhibited a broad proinflammatory cytokine response at four and forty-eight hours. CONCLUSIONS Platelet-rich plasma was shown to contain a mixture of anabolic and catabolic mediators. Synoviocytes treated with platelet-rich plasma responded with substantial MMP secretion, which may increase cartilage catabolism. Synoviocytes responded to PDGF with a substantial proinflammatory response.

Poster 10 Is There a Chondroprotective Effect of Autologous Platelet Integrated Concentrate (APIC) on an Osteoarthritis (OA) Rabbit Model? A Pilot Study

exam, was otherwise normal. He was subsequently sent for radiographs of the pelvis and bilateral (B/L) hips which revealed advanced degenerative joint disease (DJD). On AP view, radiographic measurements of the neck shaft angles were found to be greater than 142°, while lateral radiographs showed an anteverted neck in relation to the femoral shaft. Setting: Outpatient physiatry office. Results or Clinical Course: The radiographic findings, in combination with clinical presentation, helped confirm the diagnosis of B/L pistol grip hip deformity (PGD). Such deformity led to severe progressive DJD, which limited both ROM and the performance of activities of daily living. As a result, the patient underwent B/L total hip arthroplasty (THA) without complication. Discussion: PGD is a pre-arthritic condition with a greater prevalence in adults who are younger than 50 years old and are very physically active. Such patients presenting with groin pain and decreased hip ROM should be evaluated for PGD. The triad of Cam type anterior femoral acetabular impingement, DJD, and a femoral neck-shaft angle 140° or 115° with radiographic evidence of an abnormally shaped femoral head is suggestive of PGD. Significant benefit may arise from early recognition and orthopedic evaluation in terms of diagnosis and treatment. Conclusions: PGD left untreated is progressive and ultimately leads to THA. With early recognition, there is potential for successful treatment via arthroscopy. It is therefore imperative that the rehabilitation physician be familiar with this condition so that such a condition does not go unnoticed.

Poster 13 Can Cartilage Degradation be Prevented by Platelet Rich Plasma (PRP) Preparations on Bovine Cartilage Explants

nitisinone. Design: Prospective randomized treatment study. Setting: Biomedical research facility. Participants: 40 subjects with alkaptonuria (27 male and 13 female). Baseline 38 years old to 65 years old (mean age 51). Interventions: Nitisinone (IND 71780). Main Outcome Measures: Human activity profile (HAP), a measure of physical activity, SF-36, Health Assessment Questionnaire (HAQ), a measure of ADL and health status, Pain Disability Index (PDI), Wisconsin Brief Pain questionnaire (BP), the fatigue assessment instrument (FAI). Results: On the HAP adjusted activity score (AAS) over 3 years, the treatment group (TG) had 3 fewer subjects in the impaired category, 1 more subject in the moderately active group, and gained 2 subjects in the active group. The control group (CG) had 1 more subject in the impaired category, 1 fewer subject in the moderately active group, and no change in the active group. In controlling for the subjects’ homogentisic acid, the TG significantly increased its AAS and HAP maximum activity score (MAS) in the 3rd year (P .040 and P .032, respectively). In the TG, the AAS increased from 56.50-61.61 and the CG decreased from 64.06-63.87. In the TG, the average MAS increased from 71.22 to 73.11 and the CG average decreased from 78.44 to 76.19. On the HAQ, the TG had 2 more subjects with no functional limitations and 2 fewer with moderate limitations; the CG had 3 more with mild limitations and 3 fewer with moderated limitations. The TG and CG are associated with increased SF-36 physical composite score (PCS) (P .045 and P .043, respectively). The CG is associated with increased SF-36 mental composite score (MCS) (P .009). In the 1st year, the TG is associated with lower BP right now pain level (BPRN) (P .015) then at 3 years, both groups have lower BPRN (P .015 (TG) and P .026 (CG)). Conclusions: In a 3-year follow up of this alkaptonuria cohort, the TG is associated with an increase in maximum and average activity level. However, the TG and the CG have improvement in physical disability. Both groups have a lower pain level at 3 years but the TG had a significant earlier reduction in pain. Further long-term treatment studies are warranted to determine if nitisinone treatment is associated with improvement in activity, pain, and disability over time.

Poster 8 hondroprotective Effect of Alpha-2-Macroglobulin (A2M) on Bovine Cartilage Explants

due to low prevalence, severe cognitive and functional deficits, and poor prognosis at time of diagnosis. Conclusions: Those suffering PML are often left with severe disabilities and may benefit from an intense multidisciplinary rehabilitation program to improve function and enhance quality of life. Inpatient rehabilitation also allows for daily monitoring of response to HAART and potential dangerous complications such as immune reconstitution inflammatory syndrome.