ABSTRACT
PURPOSE: Damage of the knee cartilage is a common condition manifesting itself mainly by pain and/or swelling that may substantially reduce the quality of life while ultimately leading to osteoarthritis in affected patients. Here, we aimed to evaluate the safety and efficacy of cultured autologous bone marrow mesenchymal stem cells (BM-MSCs) attached to the 3D Chondrotissue® scaffold by autologous blood plasma coagulation (BiCure® ortho MSCp) in the treatment of knee cartilage defects. METHODS: The primary endpoint of this phase I/IIa clinical trial was to evaluate the safety of the treatment. The secondary objective was to determine the short-to-medium-term therapeutic outcomes by standardized scoring questionnaires including Lysholm Knee Scoring Scale (Lysholm score), Knee Injury and Osteoarthritis Outcome Score (KOOS), and pain Visual Analogue Scale (VAS) systems and imaging (X-ray and magnetic resonance imaging, MRI). A total of six patients were included and followed for 12 months after the surgery. RESULTS: BiCure® ortho MSCp was well tolerated with no adverse events associated with the investigational medicinal product. Significant improvements were observed in Lysholm scores and KOOS while X-ray showed no deterioration of the arthritis and MRI revealed a persistent filling of the chondral defects by the implant. CONCLUSION: Overall, our data demonstrate the safety of the tested investigational medicinal product. The function of the treated knee improved within one year after surgery in all enrolled patients. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: EudraCT No.: 2018-004,067-31; October 18 2018.
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a progressive untreatable neurodegenerative disorder, leading to the death of the cortical and spinal motoneurons (MNs). Bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) may represent a new approach to slowing down the progression of ALS by providing neurotrophic support to host MNs and by having an anti-inflammatory effect. We have designed a prospective, nonrandomized, open-label clinical trial (phase I/IIa, EudraCT No. 2011-000362-35) to assess the safety and efficacy of autologous multipotent BM-MSCs in ALS treatment. Autologous BM-MSCs were isolated and expanded under GMP conditions. Patients received 15 ± 4.5 × 106 of BM-MSCs via lumbar puncture into the cerebrospinal fluid. Patients were monitored for 6 months before treatment and then for an 18-month follow-up period. Potential adverse reactions were assessed, and the clinical outcome was evaluated by the ALS functional rating scale (ALSFRS), forced vital capacity (FVC), and weakness scales (WSs) to assess muscle strength on the lower and upper extremities. In total, 26 patients were enrolled in the study and were assessed for safety; 23 patients were suitable for efficacy evaluation. After intrathecal BM-MSC application, about 30% of the patients experienced a mild to moderate headache, resembling the headaches after a standard lumbar puncture. No suspected serious adverse reactions (SUSAR) were observed. We found a reduction in ALSFRS decline at 3 months after application (p < 0.02) that, in some cases, persisted for 6 months ( p < 0.05). In about 80% of the patients, FVC values remained stable or above 70% for a time period of 9 months. Values of WS were stable in 75% of patients at 3 months after application. Our results demonstrate that the intrathecal application of BM-MSCs in ALS patients is a safe procedure and that it can slow down progression of the disease.