K. Zaslav (New York, US)Lenox Hill Orthopedic Institute Center for Regenerative Orthopaedic Medicine
Presenter Of 5 Presentations
9.1.1 - The Science: Osteochondral Remodeling Using Aragonite-Based Implants
10.3.10 - A RCT of a Single, Intra-Articular Injection of Autologous Protein Solution(APS) in Patients With Knee Osteoarthritis (PROGRESS IV)
The purpose of this study is to determine the safety and effectiveness of a single injection of nSTRIDE® APS for unilateral knee osteoarthritis (NCT02905240).
Methods and Materials
This study was conducted as an Investigational Device Exemption (IDE-17069) with the FDA. Subjects with knee OA Kellgren-Lawrence 2-4 (n=332) were randomized to receive a single intra-articular injection of APS or saline under ultrasound guidance. The primary endpoint was the change in WOMAC pain from baseline to 12-months post-injection. Secondary endpoints included functional status, knee stiffness, and quality of life. Injection safety and anatomical changes were evaluated by MRI and radiographs 12 months post-injection.
APS treatment showed a significant improvement in WOMAC Pain compared to baseline (51.8±36.2% improvement [95% CI 46.0, 57.7]) 12 months after a single injection, however, no significant difference in treatment effect between APS and saline was observed. No statistical differences in adverse event reporting between groups occurred. There was significant improvement at 12 months from baseline in function, stiffness, VAS pain, and EQ-5D for both groups. No major changes in joint morphology were shown for either group, as assessed by x-ray and MRI. By 12-months post-injection, saline subjects took more rescue medication, restricted medication, and exited due to knee pain at almost twice the rate of APS subjects. A novel post hoc pain responder criteria was created that accounted for medication usage and study exit rate, which demonstrated a statistically significant difference in responder rates(p=0.0239)(Figure 1).
Treatment with a single, intra-articular injection of APS in subjects with knee osteoarthritis can be considered safe, and was found to reduce pain and improve function up to 12 months when compared to baseline. A novel responder criterion incorporating medication usage was developed that could be used in future studies as a method to help mitigate the high placebo response typically observed in knee OA studies.
P205 - Evaluating the Efficacy of Scaffold-Based Exosome Delivery Based on Changes in Exosome Activity
The purpose of this study was to compare the activities of fresh, lyophilized, and cultured mesenchymal stem cell-derived exosomes (MSC-exos) to evaluate the viability of scaffold-based exosome delivery for the treatment of osteoarthritis (OA) of the knee joint.
Methods and Materials
MSC-exos were harvested from human adipose tissue stem cells and separated into three groups: the first was cultured at 37° C for one week, the second was lyophilized, and the third was snap-frozen. Cultured primary human articular chondrocytes were seeded onto a 24-well plate and exposed to human interleukin 1-beta (IL-1β) to stimulate OA conditions. The three exosome aliquots were selectively added to the wells and relative fold gene expression was obtained for the following genes: 1) ACAN, 2) COL2, 3) IL-1, 4) MMP-13, and 5) TNF-α.
There was no significant difference in ACAN gene expression between the OA only group and all three exosome-treated groups. The addition of exosomes helped increase COL2 levels in all three exosome-treated groups when compared to the OA only group. In particular, the OA + lyophilized exosomes (p = 0.019) and OA + cultured exosomes (p < 0.001) groups displayed significant increases in COL2. The OA condition triggered significant gene expression of IL-1 and TNF-α in the OA only group, but these levels were significantly reduced in all three exosome treated groups (fresh: p = 0.012, p < 0.005; lyophilized: p = 0.012, p < 0.005; cultured: p = 0.012, p < 0.005). Lastly, there was a significant difference in relative fold gene expression of MMP-13 between the OA only group and all three exosome-treated groups (fresh: p = 0.001, lyophilized: p = 0.002, cultured: p = 0.003).
Our results indicate that scaffolds that require lyophilization and/or display prolonged degradation rates can be used as viable drug delivery vehicles for exosomes into the knee joint.