Phase I Clinical Trial of UC-MSCs in the Treatment of Knee Osteoarthritis

Inclusion Criteria:

• Prior to conducting any assessment, written informed consent must be obtained;

• Able to communicate well with researchers during screening, understand and complywith experimental requirements;

• Age range from 50 to 70 years old (including threshold), regardless of gender;

• Male weight ≥ 50 kg, female weight ≥ 45 kg, body mass index (BMI) within the rangeof 18-26 kg/m2 (including critical values);

• According to the diagnostic criteria for knee osteoarthritis in the "Guidelines forthe Diagnosis and Treatment of Osteoarthritis (2018 Edition)", subjects diagnosedwith knee osteoarthritis (see Annex 1 for details); The course of kneeosteoarthritis is more than 4 weeks;

• The target knee joint X-ray Kellgren Lawrence radiological grading (K-L IV grade) isII-III grade. Patients diagnosed with knee osteoarthritis on both sides should havenon target knee joint symptoms, signs, and grading that do not exceed the targetknee joint;

• MRI examination shows partial or full layer damage to the cartilage of the kneejoint;

• A VAS score of ≥ 5 and ≤ 7 for knee joint pain at least 48 hours after discontinuingthe use of all painkillers during screening;

• Patients who use analgesic therapy (taking paracetamol/acetaminophen) to controllocal pain in the target knee joint agree to discontinue the use of similaranalgesics 2 weeks prior to administration, and only allow NSAID as a rescue drug;Patients who use glucosamine, chondroitin, opioid drugs, or diacetate, glucosamine,etc. must agree to discontinue such drugs from 2 weeks prior to administration.

Exclusion Criteria:

• Individuals with a history of knee joint infection, surgery, and radiation therapywithin 6 months prior to administration;

• Combined instability of the knee joint (anterior and posterior cruciate ligaments,medial and lateral collateral ligaments), rupture, relaxation, or external deformityof the knee joint;

• According to researchers, diseases that may interfere with knee joint functionassessment, such as symptomatic lower back pain, lumbar disc herniation, and hipjoint pain in the target knee joint;

• According to the judgment of researchers, local diseases that may confuse knee jointfunction assessment include but are not limited to septic arthritis, reactivearthritis, clinically recurrent pseudogout, chondrocalcinosis, or joint fractures;

• Within 3 months prior to administration, any medication injection treatment (including intra-articular injection of growth factors, hormones, or sodiumhyaluronate) or lavage surgery has been received in the knee joint (target side)cavity;

• Merge intra-articular or periarticular tumors (such as knee synovial chondroma,pigmented nodular synovitis, etc.);

• Various serious systemic diseases such as neurological disorders, respiratorydisorders, heart diseases (NYHA grade III and above), and liver dysfunction (ALT>3) × ULN or AST>3 × ULN, renal dysfunction (Cr>2) × ULN or BUN>2 × ULN, coagulationdysfunction (INR>1.5), or severe hematological disorders (such as grade 3 or aboveanemia, hemoglobin (Hb)<8 g/dL, grade 2 or above thrombocytopenia, PLT<75) × 10 ^ 9/L);

• Diagnosed as systemic inflammatory arthritis or connective tissue disease, includingbut not limited to rheumatoid arthritis, psoriatic arthritis, ankylosingspondylitis, gout, Paget's disease, systemic lupus erythematosus, or other systemicdiseases that may confuse KOA assessment (such as fibromyalgia);

• Subjects who receive long-term (>14 days) oral corticosteroids>5 mg/day within 3months prior to administration, or who require long-term glucocorticoid treatmentduring the trial period;

• Previously received stem cell therapy;

• Uncontrolled hypertension is defined as systolic blood pressure (SBP)>160 mmHg ordiastolic blood pressure (DBP)>100 mmHg during screening;

• Having a history of tumors, mental illness, severe autoimmune diseases,hematological diseases, and long-term use of immunosuppressants;

• Have a history of alcohol and prohibited drug abuse;

• Has a history of hypersensitivity to protein drugs;

• There are contraindications to MRI examination or unwillingness to undergo MRIexamination;

• Hepatitis B, hepatitis C, AIDS, syphilis serological test positive pathogens;

• Pregnant or lactating women, or male or female patients who tested positive forblood pregnancy during screening or have planned childbirth within 3 months aftermedication;

• Patients who have received live vaccines or attenuated live vaccines within onemonth before administration;

• Patients who have participated in clinical trials of other drugs or devices within 3months prior to administration;

• Patients with poor compliance, poor communication skills, inability to adhere tofollow-up, and inability to complete the entire trial;

• The researchers believe that it is not suitable for participants to enter thisexperiment.