Our laboratory has recently characterized a population of cells from adipose tissue, termed processed lipoaspirate (PLA) cells, which have multi-lineage potential similar to bone-marrow-derived mesenchymal stem cells (MSCs). This study is the first comparison of PLA cells and MSCs isolated from the same patient. No significant differences were observed for yield of adherent stromal cells, growth kinetics, cell senescence, multi-lineage differentiation capacity, and gene transduction efficiency. Adipose tissue is an abundant and easily procured source of PLA cells, which have a potential like MSCs for use in tissue-engineering applications and as gene delivery vehicles.

Products from commercially available PRP separation systems produce differing concentrations of growth factors and WBCs. Further research is necessary to determine the clinical relevance of these findings.

Background: Previous studies have shown improvement in patellar tendinopathy symptoms after platelet-rich plasma (PRP) injections, but no randomized controlled trial has compared PRP with dry needling (DN) for this condition. Purpose: To compare clinical outcomes in patellar tendinopathy after a single ultrasound-guided, leukocyte-rich PRP injection versus DN. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 23 patients with patellar tendinopathy on examination and MRI who had failed nonoperative treatment were enrolled and randomized to receive ultrasound-guided DN alone (DN group; n = 13) or with injection of leukocyte-rich PRP (PRP group; n = 10), along with standardized eccentric exercises. Patients and the physician providing follow-up care were blinded. Participants completed patient-reported outcome surveys before and at 3, 6, 9, 12, and ≥26 weeks after treatment during follow-up visits. The primary outcome measure was the Victorian Institute of Sports Assessment (VISA) score for patellar tendinopathy at 12 weeks, and secondary measures included the visual analog scale (VAS) for pain, Tegner activity scale, Lysholm knee scale, and Short Form (SF-12) questionnaire at 12 and ≥26 weeks. Results were analyzed using 2-tailed paired and unpaired t tests. Patients who were dissatisfied at 12 weeks were allowed to cross over into a separate unblinded arm. Results: At 12 weeks after treatment, VISA scores improved by a mean ± standard deviation of 5.2 ± 12.5 points ( P = .20) in the DN group (n = 12) and by 25.4 ± 23.2 points ( P = .01) in the PRP group (n = 9); at ≥26 weeks, the scores improved by 33.2 ± 14.0 points ( P = .001) in the DN group (n = 9) and by 28.9 ± 25.2 points ( P = .01) in the PRP group (n = 7). The PRP group had improved significantly more than the DN group at 12 weeks ( P = .02), but the difference between groups was not significant at ≥26 weeks ( P = .66). Lysholm scores were not significantly different between groups at 12 weeks ( P = .81), but the DN group had improved significantly more than the PRP group at ≥26 weeks ( P = .006). At 12 weeks, 3 patients in the DN group failed treatment and subsequently crossed over into the PRP group. These patients were excluded from the primary ≥26-week analysis. There were no treatment failures in the PRP group. No adverse events were reported. Recruitment was stopped because interim analysis demonstrated statistically significant and clinically important results. Conclusion: A therapeutic regimen of standardized eccentric exercise and ultrasound-guided leukocyte-rich PRP injection with DN accelerates the recovery from patellar tendinopathy relative to exercise and ultrasound-guided DN alone, but the apparent benefit of PRP dissipates over time.

Background: Numerous studies have shown platelet-rich plasma (PRP) preparations differ with respect to the inclusion of certain blood components, which may affect the host’s cellular response. Hypothesis: This study evaluated the inflammatory effect of Biomet GPS III leukocyte-rich PRP (LR-PRP) versus MTF Cascade leukocyte-poor PRP (LP-PRP) after intratendinous injection in an animal model. The authors anticipated that LR-PRP would incite a greater acute inflammatory response than LP-PRP. Study Design: Controlled laboratory study. Methods: A total of 17 skeletally mature New Zealand White rabbits were tested. In all cases, healthy patellar tendons were treated. In the control animals, one patellar tendon was injected with 2 mL autologous whole blood, and the other was injected with 2 mL sterile saline. Seven total tendons were injected with whole blood, and 7 tendons were injected with saline. In the experimental animals, one patellar tendon was injected with 2 mL LR-PRP, and the other was injected with 2 mL LP-PRP. Ten tendons were injected with LR-PRP, and 10 tendons were injected with LP-PRP. Animals were euthanized at 5 or 14 days after injection. Tendons were harvested and stained using hematoxylin and eosin and scored semi-quantitatively for total white blood cells (WBCs), mononuclear cells (macrophages and lymphocytes), polymorphonuclear cells (PMNs), vascularity, fiber structure, and fibrosis. Results: At 5 days after injection, tendons treated with LR-PRP had significantly greater overall tendon scores (6.3 ± 1.79 vs 1.8 ± 1.64, P = .012), as well as mean scores for fiber structure (1.4 ± 0.22 vs 0.50 ± 0.50, P = .012), denoting disrupted composition, total WBCs (1.1 ± 0.89 vs 0.10 ± 0.22, P = .014), mononuclear cells (macrophages and lymphocytes) (0.80 ± 0.45 vs 0.10 ± 0.22, P = .014), vascularity (1.7 ± 0.27 vs 0.80 ± 0.16, P = .008), and fibrosis (1.0 ± 0.35 vs 0.3 ± 0.45, P = .037) compared with tendons treated with LP-PRP. Otherwise, there were no significant differences in mononuclear cells ( P = .590), PMN cells ( P = 1.00), total WBCs ( P = .811), vascularity ( P = .650), or total tendon score ( P = .596) in any of the treatment groups at 14 days. Conclusion: Compared with leukocyte-poor Cascade PRP, leukocyte-rich GPS III PRP causes a significantly greater acute inflammatory response at 5 days after injection. There is no significant difference in the inflammatory response or cellularity regardless of the injection type at 14 days after intratendinous injection. Clinical Relevance: Platelet-rich plasma injections are frequently prepared using commercial systems and are administered for clinical treatment of chronic tendinopathy. It is important to characterize the cellular responses elucidated by different injection preparations to further understand their effect on tissue healing and aid clinical decision making. Future investigations are necessary to apply these findings to the clinical setting.

Background:Intra-articular (IA) corticosteroid therapy has been used for the treatment of inflammation and pain in the knee since the 1950s.Purpose:To review the current literature on the effects of IA corticosteroids on articular cartilage.Study Design:Systematic review.Methods:A MEDLINE and SCOPUS database search was performed, and studies were selected for basic science and clinical trial research on corticosteroids with direct outcome measures of cartilage health. Preliminary searches yielded 1929 articles, and final analysis includes 40 studies.Results:Methylprednisolone, dexamethasone, hydrocortisone, betamethasone, prednisolone, and triamcinolone were reported to display dose-dependent deleterious effects on cartilage morphology, histology, and viability in both in vitro and in vivo models. The beneficial animal in vivo effects of methylprednisolone, hydrocortisone, and triamcinolone occurred at low doses (usually <2-3 mg/dose or 8-12 mg/cumulative total dose in vivo), at which increased cell growth and recovery from damage was observed; the single human clinical trial indicated a beneficial effect of triamcinolone. However, at higher doses (>3 mg/dose or 18-24 mg/cumulative total dose in vivo), corticosteroids were associated with significant gross cartilage damage and chondrocyte toxicity. Dose and time dependency of corticosteroid chondrotoxicity was supported in the in vitro results, however, without clear dose thresholds.Conclusion:Corticosteroids have a time- and dose-dependent effect on articular cartilage, with beneficial effects occurring at low doses and durations and detrimental effects at high doses and durations. Clinically, beneficial effects are supported for IA administration, but the lowest efficacious dose should be used.

ultipotential processed lipoaspirate (PLA) cells extracted from five human infrapatellar fat pads and embedded into fibrin glue nodules, were induced into the chondrogenic phenotype using chondrogenic media. The remaining cells were placed in osteogenic media and were transfected with an adenovirus carrying the cDNA for bone morphogenetic protein-2 (BMP-2). We evaluated the tissue-engineered cartilage and bone using in vitro techniques and by placing cells into the hind legs of five severe combined immunodeficient mice.After six weeks, radiological and histological analysis indicated that the PLA cells induced into the chondrogenic phenotype had the histological appearance of hyaline cartilage. Cells transfected with the BMP-2 gene media produced abundant bone, which was beginning to establish a marrow cavity. Tissueengineered cartilage and bone from infrapatellar fat pads may prove to be useful for the treatment of osteochondral defects. [Br] 2003;85-B:740-7. J Bone Joint Surg

Background The effect of platelet-rich plasma (PRP) on chondrocytes has been studied in cell and tissue culture, but considerably less attention has been given to the effect of PRP on synoviocytes. Fibroblast-like synoviocytes (FLS) compose 80% of the normal human synovium and produce cytokines and matrix metalloproteinases that can mediate cartilage catabolism. Purpose To compare the effects of leukocyte-rich PRP (LR-PRP), leukocyte-poor PRP (LP-PRP), red blood cell (RBC) concentrate, and platelet-poor plasma (PPP) on human FLS to determine whether leukocyte and erythrocyte concentrations of PRP formulations differentially affect the production of inflammatory mediators. Study Design Controlled laboratory study. Methods Peripheral blood was obtained from 4 donors and processed to create LR-PRP, LP-PRP, RBCs, and PPP. Human synoviocytes were cultured for 96 hours with the respective experimental conditions using standard laboratory conditions. Cell viability and inflammatory mediator production were then evaluated. Results Treatment with LR-PRP resulted in significantly greater synoviocyte death (4.9% ± 3.1%) compared with LP-PRP (0.72% ± 0.70%; P = .035), phosphate-buffered saline (PBS) (0.39% ± 0.27%; P = .018), and PPP (0.26% ± 0.30%; P = .013). Synoviocytes treated with RBC concentrate demonstrated significantly greater cell death (12.5% ± 6.9%) compared with PBS (P < .001), PPP (P < .001), LP-PRP (P < .001), and LR-PRP (4.9% ± 3.1%; P < .001). Interleukin (IL)–1β content was significantly higher in cultures treated with LR-PRP (1.53 ± 0.86 pg/mL) compared with those treated with PBS (0.22 ± 0.295 pg/mL; P < .001), PPP (0.11 ± 0.179 pg/mL; P < .001), and RBCs (0.64 ± 0.58 pg/mL; P = .001). IL-6 content was also higher with LR-PRP (32,097.82 ± 22,844.300 pg/mL) treatment in all other groups (P <.001). Tumor necrosis factor–α levels were greatest in LP-PRP (9.97 ± 3.110 pg/mL), and this was significantly greater compared with all other culture conditions (P < .001). Interferon-γ levels were greatest in RBCs (64.34 ± 22.987 pg/mL) and significantly greater than all other culture conditions (P <.001). Conclusion Treatment of synovial cells with LR-PRP and RBCs resulted in significant cell death and proinflammatory mediator production. Clinical Relevance Clinicians should consider using leukocyte-poor, RBC-free formulations of PRP when administering intra-articularly.

Purpose of Review This review evaluates current clinical literature on the use of platelet-rich plasma (PRP), including leukocyterich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP), in order to develop evidence-based recommendations for various musculoskeletal indications. Recent Findings Abundant high-quality evidence supports the use of LR-PRP injection for lateral epicondylitis and LP-PRP for osteoarthritis of the knee. Moderate high-quality evidence supports the use of LR-PRP injection for patellar tendinopathy and of PRP injection for plantar fasciitis and donor site pain in patellar tendon graft BTB ACL reconstruction. There is insufficient evidence to routinely recommend PRP for rotator cuff tendinopathy, osteoarthritis of the hip, or high ankle sprains. Current evidence demonstrates a lack of efficacy of PRP for Achilles tendinopathy, muscle injuries, acute fracture or nonunion, surgical augmentation in rotator cuff repair, Achilles tendon repair, and ACL reconstruction. Summary PRP is a promising treatment for some musculoskeletal diseases; however, evidence of its efficacy has been highly variable depending on the specific indication. Additional high-quality clinical trials with longer follow-up will be critical in shaping our perspective of this treatment option.