ObjectiveTo investigate the safety and efficacy of human umbilical cord mesenchymal stem cells (MSCs) by intra-articular injection for degenerative knee osteoarthritis. MethodsBetween January 2015 and January 2016, 36 patients with moderate or severe degenerative knee osteoarthritis were randomly devided into 2 groups (n=18). Intra-articular injection of 2.5-3.0 mL human umbilical cord MSCs suspension containing (2-3)×107 cells was performed once a month for 2 times as a course of treatment in the cell treatment group; sodium hyaluronate by intra-articular injection was used once a week for 5 times as a course of treatment in the control group. There was no significant difference in gender, age, body mass index, side, stage of osteoarthritis, course of disease, and preoperative Lysholm score of the knee joint, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), and SF-36 scale score between 2 groups (P > 0.05). The clinical efficacy was evaluated by SF-36 scale score, Lysholm score, and WOMAC score. ResultsAll patients of 2 groups received a course of treatment. The patients were followed up for 6 months. After injection, the incidences of pain and swelling in the cell treatment group were significantly higher than those in the control group (χ2=16.200, P=0.000; χ2=11.688, P=0.000), but no significant difference was found in the incidence of effusion (χ2=2.118, P=0.146). In the cell treatment group, Lysholm score at 1-6 months after treatment, WOMAC score and SF-36 scale score at 2-6 months after treatment were significantly better when compared with scores before treatment (P < 0.05), and no recurrence of knee pain was observed during follow-up. In the control group, there was no significant difference in Lysholm score and SF-36 scale score between pre-and post-treatment (P > 0.05); there were significant differences in WOMAC score between pre-treatment and at 1, 2, 3 months after treatment (P < 0.05); at 3 months after treatment, 11 patients had joint pain symptoms again. No significant difference was found in the knee joint function score and SF-36 scale score at 1 and 2 months after treatment between 2 groups (P > 0.05), but the scores of the cell treatment group were significantly better than those of the control group at 3 and 6 months (P < 0.05). ConclusionIt can significantly improve the joint function and quality of life to use intra-articular injection of human umbilical cord MSCs for treating degenerative knee osteoarthritis. It takes effect after 1 month and the treatment effect can be sustained for 6 months.