First-in-human and multicenter phase I study of OSCA therapy for knee osteoarthritis

www.nature.com/emm ARTICLE OPEN First-in-human and multicenter phase I study of OSCA therapy for knee osteoarthritis Dae Keun Suh1,10, Sang Hak Lee2,10, Yohan Bae3, Hee-Jin Kang3, Seunghee Lee4, Mijin Kim4, JongCheon Na3, Ali Mobasheri ✉ ✉ Kyung-Sun Kang 4,9 and Kyoung Ho Yoon1 5,6,7,8 , © The Author(s) 2026 1234567890();,: Knee osteoarthritis is a degenerative joint disease, with no fundamental cure beyond pain relief and anti-inflammation. This phase I, multicenter, open-label, dose-escalation trial evaluated the safety, tolerability, and preliminary efficacy of OSCA, an intra-articular injection co-formulation of osiramestrocel (allogeneic mesenchymal stromal cells) and cartilage acellular matrix, in patients with Kellgren–Lawrence (K&L) grade 2 or 3 knee osteoarthritis. Twelve patients received a single intra-articular injection of OSCA at low (2.5 × 107 cells, n = 3), mid (5.0 × 107 cells, n = 3), or high (1.0 × 108 cells, n = 6) doses; cell concentration was 3.3 × 107 cells/ml for all cohorts, and cartilage acellular matrix was 60 mg (40 mg/ml). The primary end point was safety, assessed by dose-limiting toxicities and TEAEs. Secondary end points included Visual Analog Scale (VAS), International Knee Documentation Committee (IKDC), Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART), Whole-Organ Magnetic Resonance Imaging Score (WORMS), and K&L grading over 24 weeks. OSCA was well tolerated, with no dose-limiting toxicities and mild-to-moderate TEAEs in 25.0% (3/12) of patients. At 24 weeks, mid-dose and high-dose groups showed numerically greater improvement in pain and function than the low-dose group (P < 0.05), with up to 91.3% reduction in VAS (P = 0.002) and 102.7% IKDC (P = 0.005). MRI outcomes showed efficacy signals: MOCART total scores improved in 70% of patients, WORMS cartilage integrity improved in 50%, and K&L grades remained stable in 80%. Overall, these findings support the feasibility and tolerability of a single OSCA injection, with exploratory efficacy in both clinical and MRI outcomes. Experimental & Molecular Medicine; https://doi.org/10.1038/s12276-026-01728-w INTRODUCTION Osteoarthritis is a degenerative joint disease characterized by progressive cartilage loss, subchondral bone remodeling, synovial inflammation, and joint pain, ultimately leading to functional impairment and disability1,2. Osteoarthritis, a leading cause of chronic pain and disability worldwide, sustantially impairs the quality of life of patients and imposes a major socioeconomic burden3,4. Despite its prevalence, osteoarthritis still lacks treatments that modify disease progression or restore joint function. Current therapies — analgesics, non-steroidal anti-inflammatory drugs, and intra-articular (IA) injections — mainly target symptomatic relief, as no disease-modifying osteoarthritis drug (DMOAD) has been approved5–7. Recently, mesenchymal stem cell (MSC)-based therapies have demonstrated potential for cartilage protection and regeneration in osteoarthritis8–12. However, structural recovery in the knee joint, such as cartilage repair and subchondral bone regions, has not been consistently demonstrated in clinical studies. Among them, studies using MSCs have shown either no meaningful changes in bone marrow lesions or cartilage morphology, or only limited evidence of cartilage regeneration in short-term follow-up13–15. Among various MSC sources, human umbilical cord blood-derived MSCs stand out as a promising regenerative therapy for osteoarthritis owing to their high proliferative capacity, low immunogenicity, and secretion of bioactive factors that facilitate cartilage repair and modulate the joint microenvironment11,12,16. Therefore, to date, no approved DMOAD effectively stops disease progression, preserves joint structure, and improves physical function beyond pain relief. OSCA is a novel therapy, a co-formulation of OSiramestrocel (human umbilical cord blood-derived allogeneic mesenchymal stromal cells) and Cartilage Acellular matrix (CAM) that enhances cartilage regeneration through their synergistic interaction. As small animal models such as rabbits and rats have excellent selfhealing ability, it is difficult to expect equivalent efficacy in actual clinical practice17,18. Therefore, for the clinical application, it is required to evaluate the therapeutic efficacy, stability, and biological safety in large animal models that have less self-healing 1 Department of Orthopaedic Surgery, Kyung Hee University Hospital 23, Seoul, Republic of Korea. 2Department of Orthopaedic Surgery, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea. 3Kangstem Biotech Co., Ltd, Hongwoo Building, Seoul, Republic of Korea. 4Stem Cell and Regenerative Bioengineering Institute, Global R&D Center, Kangstem Biotech Co. Ltd, Seoul, Republic of Korea. 5Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland. 6 Department of Personalized Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania. 7Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China. 8Faculté de Médecine, Université de Liège, Quartier Hôpital — Avenue Hippocrate 15 (Bât. B36), Liège, Belgium. 9 Adult Stem Cell Research Center, and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. 10These authors contributed equally: Dae Keun Suh, Sang Hak Lee. ✉email: ; Received: 8 September 2025 Revised: 30 January 2026 Accepted: 5 March 2026 D.K. Suh et al. 2 Fig. 1 Details of study protocol and flow diagram. This figure illustrates the study design, including participant allocation, follow-up schedule, and assessment timeline. Fourteen patients with knee osteoarthritis were screened and allocated to three cohorts: low-dose (n = 3), middle-dose (n = 3), and high-dose (n = 6). Two patients from the high-dose cohort discontinued participation owing to contraindicated medication use (n = 1) and adverse events (n = 1). All remaining participants completed follow-up assessments over 24 weeks. Assessments were conducted on day 1 and at weeks 1, 4, 8, 12, 16, 20, and 24 post-intra-articular OSCA administration to assess safety and exploratory efficacy via pain and function scores. Radiological exploratory end points were evaluated at baseline and at 24 weeks, whereas biomarker analyses were conducted at baseline and weeks 1, 4, 12, and 24. DLT, dose-limiting toxicity. ability and better mimic the anatomical features of human articular joints19–21. Our previous study demonstrated that IA OSCA injections sustantially promoted cartilage repair, modulated the joint microenvironment, reduced inflammation, and supported subchondral bone remodeling, which highlighted their potential as a DMOAD22,23. Therefore, this first-in-human phase I study aims to evaluate the safety and tolerability of OSCA and its (...truncated)