Human umbilical cord mesenchymal stem cells in the treatment of knee osteoarthritis: study protocol for a clinical trial / 中国组织工程研究

ABSTRACT

BACKGROUND: Osteoarthritis (OA) is a kind of chronic bone and joint disease which seriously endangers human health. Cell therapy for OA has aroused widespread concern and gotten rapid development in recent years. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have the advantages of easy amplification and differentiation, anti-inflammation and recruiting function such as MSCs from other sources. Furthermore, UC-MSCs are young cells that have large quantity, no ethical problems, high proliferative potential and pluripotent differentiation. UC-MSCs have been the most commonly used seed cells in clinical cell therapy. OBJECTIVE: To evaluate the efficacy and safety of UC-MSCs in the treatment of human knee OA to provide theoretical and clinical basis for stem cell therapy of OA. METHODS: The trail will be completed in Arthritis Clinic & Research Center, Beijing, China. Participants will be recruited according to established inclusion/exclusion criteria after obtaining the informed consent and the approval of the Ethics Committee (the first and second parts of the trial have been registered (https://register.clinicaltrials.gov/), with the identifier No. NCT03357770 and NCT03358654, and the third part will be carried out according to the conclusion of the first and second parts). The clinical trial will be divided into three parts: in the first part three groups will be recruited. Each group will contain three participants. The three groups of participants will be treated with high, medium and low dose of MSCs, respectively. Participants will be followed up to evaluate dose-limiting toxicity so as to determine the maximum tolerated dose. The second part will be a single-arm clinical trial. Nine participants will be recruited. The injection dose will be the maximum tolerated dose determined in the first part. Participants will be followed up to evaluate the safety and efficacy of the treatment. The third part will be a randomized controlled trial. Participants will be randomly divided into two groups (n=7 per group) and treated with MSCs and hyaluronic acid, respectively. During the trial, evaluators, participants and interveners will be unaware of grouping information and interventions. Participants will be followed up at designed time points after treatment to evaluate the safety and efficacy of the intervention. The trial will be terminated if there are unexplained local and systemic symptoms or death according to the NCI-CTCAE criteria. EXPECTED RESULTS: With reference to the previous literature, the knee pain will be relieved, the score of knee joint function will increase, and the cartilage defect area will decrease on MRI at 1-2 years after the intervention. The trail is expected to spend 3 years and 6 months.