Intra Articular Injection of Peripheral Blood Mononuclear Cells for Knee Osteoarthritis

Inclusion Criteria: * Tibiofemoral osteophytes on x-ray (Kellgren-Lawrence grade of 2-4) * Age ≥ 40 and ≤ 80 years. * Moderate to severe knee pain * Reduced joint space width at the medial part of the knee compared to the lateral part under x-ray examination. If standing is not feasible, the same supine position must be used consistently for follow-up. * A minimal pain score of 5 measured by both NRS and VAS when walking last week. * Knee pain on most days (no less than 15 days) in the 4 weeks before screening * Patients have experienced that NSAID or opioid pain medication failed to control knee pain in the last year. * Patients have experienced that a single intra-articular injection of medicines, such as steroids, hyaluronic acid, or platelet-rich plasma, failed to control the knee pain over 6 months. * Non-invasive treatments did not control the knee pain. Conservative and non-invasive treatment regimens may include any or all of the following: initial rest, muscle relaxants, massage, and oral medications, e.g., anti-inflammatory drugs, analgesics, narcotics/opioids. * The patients have taken supervised physical and rehabilitation therapy, such as daily walking routines, therapeutic exercises, sonication, heat/cold therapy, and electric stimulation for knee pain control within the last year. Exclusion Criteria: * Patients who have taken knee, distal femur, or proximal tibia surgery. * Patients who took an intra-articular injection of medicine, such as steroids, hyaluronic acid, or platelet-rich plasma, in the last 3 months. * Reduced joint space width at the lateral part of the knee compared to the medial part under x-ray examination. * Patients who have severe varus deformity and tibiofemoral alignments are larger than 20 degrees. * Patients who cannot cooperate with the two-year follow-up. * Patients who have had tumor, infection, or trauma at the time of recruitment. * Patients with abnormal blood routine test, such as severe anemia, leukemia, sepsis, platelet dysfunction, or other blood-related diseases. * Patients who cannot agree to the withdrawal of non-steroid anti-inflammatory drugs (NSAIDs) or opioids during the trial period. * Patients who cannot cooperate with blood drawing. * The body mass index (BMI) value of the patient is higher than 30. * Female subjects who are pregnant, breastfeeding, planning to become pregnant, or unable to cooperate in contraception during the trial. * Subjects with a history of neurocognitive disorders, or those who have sought neurological consultation due to suspected dementia or memory decline * History of post-traumatic osteoarthritis. * History of rheumatoid arthritis, gouty arthritis, spontaneous osteonecrosis of the knee (SONK), or hemophilia. * Employees or family members of the PI and co-PI.