Osteoarthritis (OA) is a chronic inflammatory disease of the bone and joints, characterized by degenerative destruction of articular cartilage, subchondral bone sclerosis and osteophyte formation, and peripheral soft tissue inflammation and proliferation. Knee Osteoarthritis (KOA), which is negative and highly active, is the most common. Currently, there are approximately 1 billion KOA patients worldwide, with approximately 150 million patients in China, and the incidence rate increases with age. The clinical manifestation of KOA is repeated and prolonged bone and joint pain, which seriously affects the patient's quality of life, ultimately leading to joint structural damage and loss of function, causing a significant burden on individuals, families, and society. At present, there is a lack of effective treatment methods for KOA both domestically and internationally, and there is an urgent need to research new treatment strategies to meet clinical needs. Numerous studies have shown that local inflammation of the joint cavity and apoptosis of articular chondrocytes are the main pathological mechanisms of knee osteoarthritis. Therefore, the key to treating KOA is to inhibit the local inflammatory response of bone joints, promote chondrocyte regeneration, repair damaged joint surfaces, and restore their normal structure and function.

Mesenchymal Stem Cells (MSCs) are the most widely studied pluripotent stem cells. It exists in various tissues, has multidirectional differentiation potential, homing effect and powerful paracrine function, can regulate tissue microenvironment, promote damaged tissue repair through cell replacement, promote in-situ cell regeneration, anti-inflammatory and immune regulation and other mechanisms. Therefore, mesenchymal stem cell therapy has become the focus of KOA new therapy research. A large number of studies have shown that MSCs can be induced to differentiate into stable mature chondrocytes that can express proteoglycan and type II collagen. Fluorescently labeled MSCs could still be detected 10 weeks after injection into the joint cavity of osteoarthritis model animals, suggesting that MSCs homed in the injured articular cartilage tissue and participated in the regeneration and repair of the injured tissue. The effectiveness of MSCs therapy for KOA has been demonstrated in osteoarthritis models in different animals including rats, rabbits, sheep, pigs, and monkeys. MSCs from different sources can effectively inhibit the inflammatory response and chondrocyte injury in model animals, and stimulate the regeneration and repair of injured chondrocytes.

In this study, three dose groups are preset, which are low-dose group: 5×10\^6 cells/2.5mL; medium-dose group: 1×10\^7 cells/2.5mL; high-dose group: 2×10\^7cells/2.5mL, 9 to 18 subjects will be recruited, and will be sequential from the low-dose group to the high-dose group according to the "3+3" dose escalation principle. At least 3 subjects are enrolled in each group for the safety and tolerability test of single administration. After the last subject in each dose group completes the DLT observation period, the sponsor and the researcher jointly confirm the safety tolerance of the subjects in the previous dose group, and only after the safe tolerance is determined can the subjects enter the next dose group, so as to evaluate the safety and tolerance of human umbilical cord mesenchymal stem cell injection in the treatment of knee osteoarthritis. Recommend appropriate cell therapy dose (RP2D) for Phase II clinical trials.