Clinical Evaluation of Safety and Efficacy of a Central Current Good Manufacturing Practices Laboratory Produced Autologous Adipose-Derived Stromal Vascular Fraction Cell Therapy Product for the Treatment of Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a prevalent condition characterized by the progressive deterioration of the entire joint and has emerged as a prominent contributor to disability on a global scale. The nature of the disease and its impact on joint function significantly limit mobility and daily activities, highlighting its substantial influence on patients' overall well-being. Stromal vascular fraction (SVF) is a heterogenous, autologous cell product, containing mesenchymal stem cells, derived from the patient's subcutaneous adipose tissue with demonstrated safety and efficacy in the treatment of KOA patients. We conducted a single-arm, open-label, multisite, FDA approved clinical study in Kellgren-Lawrence severity grade 2-4 KOA patients. The cellular product was manufactured from patient-specific lipoaspirate in a centrally located FDA-compliant manufacturing facility. Twenty-nine subjects were treated with a quality tested single intra-articular injection of GMP manufactured SVF. Adverse events, laboratory values, vital signs, and physical examination findings were monitored during the study period. Robust tolerability, without any substantial safety issues, was demonstrated. Knee pain and function, assessed through the Knee Injury and Osteoarthritis Outcome Score (KOOS), demonstrated notable improvements. These positive benefits persisted for up to 12 months, and the majority of participants expressed satisfaction. SVF from each patient was stored in a liquid nitrogen freezer for future clinical treatments. Unique to this study of autologous cells is the shipment of lipoaspirate from the clinic to a central FDA-compliant manufacturing facility for cleanroom-controlled manufacturing. The cell product characterization data demonstrate that this method produces an equivalent product in terms of cell count and viability with the added benefit of further quality assurance testing, including sterility, endotoxin, and flow cytometry, before patient administration. Clinical Trial Registration Number: NCT04043819.

Systematic Review of Platelet-Rich Plasma for Low Back Pain.

BACKGROUND: Low back pain (LBP) has a high economic burden and is strongly related to the degenerative process of the spine, especially in the intervertebral disc and of the facet joints. Numerous treatment modalities have been proposed for the management of LBP, and the use of platelet-rich plasma (PRP) has emerged as an innovative therapeutic option for degenerative disease of the spine. The present study aims to evaluate the efficacy of PRP injections in managing low back pain. METHODS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a registered at PROSPERO Systematic Reviews Platform, under number CRD42021268491. The PubMed, Web of Science, and Scopus databases were searched to identify relevant articles, along with hand searching to identify gray literature articles, with no language restrictions. Randomized clinical trials (RCTs), nonrandomized trials (NRTs), and case series (CSs) with more than 10 patients were considered eligible. The quality assessment and the risk of bias of the randomized clinical trials were evaluated using the RoB II tool. An evaluation of the description of the preparation methods was performed using an adapted version of the MIBO checklist. RESULTS: An electronic database search resulted in 2324 articles, and after the exclusion of noneligible articles, 13 RCTs and 27 NRTs or CSs were analyzed. Of the 13 RCTs, 11 found favorable results in comparison to the control group in pain and disability, one showed no superiority to the control group, and one was discontinued because of the lack of therapeutic effect at eight-week evaluation. Description of the PRP preparation techniques were found in almost all papers. The overall risk of bias was considered high in 2 papers and low in 11. An adapted MIBO checklist showed a 72.7% compliance rate in the selected areas. CONCLUSIONS: In this systematic review, we analyzed articles from English, Spanish and Russian language, from large databases and grey literature. PRP was in general an effective and safe treatment for degenerative LPB. Positive results were found in almost studies, a small number of adverse events were related, the risk of bias of the RCTs was low. Based on the evaluation of the included studies, we graded as level II the quality of the evidence supporting the use of PRP in LBP. Large-scale, multicenter RCTs are still needed to confirm these findings.

Personalized multitarget biologic injection in the spine: prospective case series of multitarget platelet-rich plasma for low back pain.

Aim: To evaluate the use of a multitarget platelet-rich plasma (PRP) injection approach for the treatment of chronic low back pain (LBP). Materials & Methods: Forty-six patients with more than 12 weeks of LBP who failed conservative treatments were injected with PRP into the facet joints, intervertebral discs, epidural space and/or paravertebral muscles. Visual analog pain scale and Roland-Morris Disability Questionnaire scores were measured at baseline and predefined intervals. Results: Mean visual analog pain scale was reduced from 8.48 to 5.17 and mean Roland-Morris Disability Questionnaire from 18.0 to 10.98 at 12 weeks (p < 0.001). These statistically significant improvements were sustained over 52 weeks. No adverse effects were observed. Conclusion: Our PRP approach demonstrated clinically favorable results and may be a promising treatment for chronic LBP.

Lay abstract Back pain can be caused by a variety of conditions. Most long-term (chronic) low back pain cases involve one or more parts of the spine causing the pain. This study describes 46 people who received injections of a blood-based substance called platelet-rich plasma into multiple parts of their spine to address chronic low back pain. The patients were followed up at several time points over the course of the following year. The results showed that the patients had improvement in their pain and disability. There was also a reduction in oral pain medication use. No unexpected medical problems were seen with this treatment. This study shows promising results for the treatment of chronic back pain.

Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee.

Objective: This study aims at evaluating the clinical effects of Platelet Rich Plasma (PRP) and Hyaluronic Acid (HA) as individual treatments for mild to moderate Osteoarthritis (OA) and it also examines the potential synergistic effects of PRP in combination with HA. Research continues to emerge examining the potential therapeutic efficacy of HA and PRP as autologous injectable treatments for joint arthritis. However, there is a paucity of research investigating the effects of combining HA and PRP on pain and functional status in patients with OA. Design: In this multi-center, randomized, controlled, double blind, prospective trial, 105 patients with mild to moderate knee osteoarthritis, who met the study criteria, were randomly allocated to one of three interventions: HA (n=36), PRP (n=36), or HA+PRP (n=33). Each patient received 3 intra-articular knee injections of their assigned substance, with 2 week intervals between each injection. Clinical outcomes were evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analogue Scale (VAS) questionnaire at baseline and after 1,3,6 and 12 months. Results: The study showed that the PRP group have significant reduction in VAS scores at 1 (p= 0.003), 3 (p= 0.0001), 6 (p= 0.0001) and 12 (p= 0.000) months when compared to HA. In addition, the PRP group illustrated greater improvement in WOMAC physical activity scale at 12 months (p= 0.008) when compared to the HA group. Combining HA and PRP resulted in a significant decreases in pain (p=0.0001) and functional limitation (p=0.0001) when compared to HA alone at 1 year post treatment; and significantly increased physical function at 1 (p=0.0004) and 3 (p=.011) months when compared to PRP alone. Conclusion: The findings of the study support the use of autologous PRP as an effective treatment of mild to moderate knee osteoarthritis. It also shows that the combination of HA and PRP resulted to better outcomes than HA alone up to 1 year and PRP alone up to 3 months. Furthermore, the results suggest that combination of PRP and HA could potentially provide better functional outcomes in the first 30 days after treatment with both PRP and HA alone.