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.

The Safety and Effectiveness of Orthobiologic Injections for Discogenic Chronic Low Back Pain: A Multicenter Prospective, Crossover, Randomized Controlled Trial with 12 Months Follow-up.

BACKGROUND: Chronic low back pain is one of the most common causes of disability, affecting more than 600 million people worldwide with major social and economic costs. Current treatment options include conservative, surgical, and minimally invasive interventional treatment approaches. Novel therapeutic treatment options continue to develop, targeting the biological cascades involved in the degenerative processes to prevent invasive spinal surgical procedures. Both intradiscal platelet-rich plasma (PRP) and bone marrow concentrate (BMC) applications have been introduced as promising regenerative treatment procedures. OBJECTIVES: The primary objective of this study is to assess the safety and effectiveness of an orthobiologic intradiscal injection, PRP or BMC, when compared to control patients. The secondary objectives are to measure: patient satisfaction and incidence of hospitalization, emergency room visit and spine surgery at predetermined follow-up intervals. STUDY DESIGN: A multicenter, prospective, crossover, randomized, controlled trial. SETTING: Comprehensive Spine and Sports Center and participating centers. METHODS: Forty patients were randomized into saline trigger point injection, intradiscal PRP, or BMC. Follow-up was 1, 3, 6, and 12 months posttreatment. Placebo patients were randomized to PRP and BMC injection if < 50% decrease in numeric rating scale (NRS) scores in 3 months, while PRP and BMC patients to the other active group if < 50% decrease in NRS scores in 6 months. RESULTS: Both PRP and BMC demonstrated statistically significant improvement in pain and function. All the placebo patients reported < 50% pain relief and crossed to the active arm. None of the patients had any adverse effects, hospitalization, or surgery up to 12 months posttreatment. LIMITATIONS: The limitations of our study were the small number of patients and open-label nature of the study. CONCLUSION: This is the only human lumbar disc study that evaluates both PRP and BMC in the same study and compares it to placebo. PRP and BMC were found to be superior to placebo in improving pain and function; however, larger randomized clinical trials are needed to answer further questions on the comparative effectiveness of various biologics as well as to identify outcome differences specific to disc pathology.