Osteoarthritis leads to articular cartilage wear, and newer therapies are aimed at slowing this degeneration. Growth factors and cytokines influence cartilage formation, and researchers are studying their use on cartilage regeneration in osteoarthritis. One method uses genetically engineered cells to deliver growth factors to damaged cartilage. This technique utilizes transforming growth factor-β proteins in modified chondrocytes to stimulate cartilage growth via an intra-articular injection. We evaluated the efficacy and outcomes of this injection on patients who had International Cartilage Repair Society grade 4 knee osteoarthritis. We evaluated 27 patients (6 men, 21 women) who had late-stage knee osteoarthritis. Patients were randomized to receive genetically engineered chondrocytes doses of 6×10(6) cells (group 1) or 1.8×10(7) cells (group 2) at a 1:1 ratio. Primary endpoints were subjective and functional evaluations, assessed by the International Knee Documentation Committee (IKDC) score. Secondary endpoints were pain severity and physical function, using the Western Ontario and McMaster osteoarthritis (WOMAC) index and the 100 mm visual analog scale (VAS). Patients were followed at 2, 4, 12, and 24 weeks postinjection. Both groups had significant improvements in outcomes. Scores improved at 12 and 24 weeks from baseline in IKDC (+10 and +14 points in group 1; +11 and +13 points in group 2), WOMAC (-12 and -13 points in group 1; -10 and -12 points in group 2), and VAS (-19 and -24 points in group 1; -20 and -20 in group 2) scores. Additionally, there were no serious adverse events, and no significant difference in adverse event incidence between the groups. Both groups expressed a mean improvement in pain, function, and physical ability following treatment injection. This modality appears to be a promising treatment for cartilage degeneration. However, further larger, multicenter, randomized studies are needed to truly evaluate the efficacy of this novel approach.

Multiple therapies have been developed to slow down the progression of knee osteoarthritis (OA), with the aim of avoiding or delaying TKA. One such potential method is cell-mediated gene therapy, which utilizes allogeneic human chondrocytes modified to express transforming growth factor-β1. Using magnetic resonance imaging (MRI), we evaluated patients who underwent treatment with this injection in a Phase II study and assessed structural changes in: (1) bone marrow edema lesions, (2) cartilage defect depth and surface area, (3) articular bone surface and osteophytes, and (4) meniscus structure and signal, as well as changes in (5) joint fluid, (6) periarticular inflammation, and (7) synovial inflammation. Twenty-seven patients (6 men and 21 women) who had late-stage OA were randomized 1:1 to receive a 3:1 mixture of nontransduced chondrocytes and genetically engineered chondrocytes, at doses of 6 × 10 cells (group 1) or 1.8 × 10 cells (group 2). MRI was performed at baseline (preinjection), and at 6 and 12 months postinjection. The whole-organ MRI score system was used to assess the aforementioned changes. Treatment was considered to be successful if patients experienced an improvement in or no change in their scores, indicating that the disease had not progressed. All patients in both cohorts individually demonstrated an improvement or no change in one or more of the assessment parameters. At 6 months, the low-dose cohort demonstrated worsening in mean scores in one parameter (bone surface and osteophytes), while the high-dose cohort demonstrated no worsening in mean scores. At 12 months, the low-dose cohort had worsening in the mean score in a subset of one parameter (cartilage signal intensity), and the high-dose cohort demonstrated worsening in mean scores in two parameters (bone surface osteophytes and periarticular inflammation). This is the first study to evaluate MRI changes in patients treated with this injection. These findings provide an impetus for further research on this topic, as well as a starting point for Phase III testing.

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Background: Novel non-operative treatment modalities, including injections of genetically engineered chondrocytes (GEC), have been developed to target the inflammatory pathways implicated in knee osteoarthritis (OA). Patient reported outcome measures (PROMs) have been the cornerstone of knee OA diagnostics and are frequently used to quantify treatment efficacy but their subjective nature limits their utility. However, inflammatory biomarkers of knee OA provide quantitative data but are less commonly used to assess the severity and progression of OA. Therefore, the purpose of this study was to correlate PROMs with biomarkers in knee OA. Specifically, we compared International Knee Documentation (IKDC) scores with serum C-terminal telopeptide of type I collagen (sCTX-I), urine C-terminal telopeptide of type II collagen (uCTX-II), and joint space width (JSW) in patients receiving GEC injections or placebo injections for knee OA.Methods: A multi-center, double-blinded, randomized, placebo-controlled study was conducted between November 2013 and August 2015. A total of 163 patients were enrolled and randomized to receive GEC injections or placebo injections in a 1:1 ratio of treatment to control. The PROMs assessed were IKDC scores which evaluated three domains: symptoms, sports and daily activity, and difference in knee function.The biomarkers assessed were sCTX-I, uCTX-II, and JSW. Outcomes were measured at baseline as well as at 6, 9, and 12 months after the injections. Scatter plots were created to graphically represent the correlations. Pearson's correlation coefficients were utilized to determine associations between IKDC scores and each of the three biomarkers.Results: Significant correlations were identified between PROMs and inflammatory biomarkers of knee OA at 6, 9, and 12 months post-treatment with GEC injections. In the GEC cohort, as IKDC scores improved, improvements in sCTX-I levels were also observed. Correlations between IKDC scores and sCTX-I levels were statistically significant at 9 months (r=−0.42, P<0.001) and 12 months (r=−0.23, P=0.049) following treatment. Additionally, there were significant correlations between IKDC scores and uCTX-II levels in the GEC cohort at 6 months (r=−0.294, P=0.011), 9 months (r=−0.383, P<0.001), and 12 months (r=−0.420, P<0.001) post-treatment. In both GEC and placebo cohorts, JSW was observed to improve as IKDC scores improved. In the GEC cohort, a statistically significant correlation was observed at 12 months post-treatment (r=0.400, P<0.001).Conclusions: Newer treatment options for knee OA target the inflammatory pathways that mediate the destruction of bone and cartilage. Inflammatory biomarkers are an objective alternative to assess the severity and progression of OA. This study found significant correlations between an established PROM (IKDC scores) and inflammatory biomarkers in knee OA (sCTX-I, uCTX-II, and JSW). For newer non-operative treatment modalities, such as GEC injections, inflammatory biomarkers of knee OA should be utilized to Lee et al. Correla...