Twenty-nine patients with symptomatic knee osteoarthritis (OA) without meniscal rupture were randomized to receive to receive one of the three knee intra-articular injections: hyaluronic acid (HA) at baseline and 6 months follow-up; umbilical-cord (UC)-derived mesenchymal stromal cells (MSCs) at baseline and 6 months follow-up (MSC-1 group; n=10); UC-MSCs at baseline followed-up by placebo at 6 months (MSC-1 group; n=10). The primary outcome of interest included the incidence of treatment-related adverse events (i.e., pain at site of injection, synovitis, septic arthritis, fever, bleeding, and urticarial lesions). Secondary outcomes of interest included the following: pain evaluated using the visual analogue scale (VAS), the Western Ontario and Mc Master Universities Arthritis Index (WOMAC) total and pain, function, and stiffness sub-scores, Whole-Organ Magnetic Resonance Imaging Score (WORMS), and the Patient Global Assessment, the Outcome Measures in Rheumatology Committee (OMER-ACT)-Osteoarthritis Research Society International (OARSI) Responder Index Criteria. All secondary outcomes were measured at 6 and 12 months follow-up. Results of this clinical trial demonstrated that no statistical significant difference was observed across all three interventions for treatment-related adverse events (p=0.99 for all). No incidence of fatal, serious, or non-serious adverse events were observed in any of the groups at 12 months follow-up. Similarly, no incidence of treatment-related adverse events of septic arthritis, fever, urticarial lesions, or bleeding were observed in any of the groups. For WOMAC total and WOMAC pain scores, scores were statistically significantly improved at 12 months in the MSC-2 group across all three interventions (p=0.04 for both). In fact, WOMAC pain and total scores in the MSC-2 group were statistically significantly improved compared to HA at 12 months follow-up (p=0.05 and p=0.04, respectively). Furthermore, VAS pain scores were statistically significantly reduced in the MSC-2 group compared to all 3 interventions (p=0.02), whereby MSC-2 vs HA was statistically significantly improved (p=0.03). No other outcomes were statistically significantly different across al three groups at any of the timepoints (p>0.05).