MSC therapy for the knee is an off-label regenerative option for patients who fail conservative management. The strongest evidence supports mild-to-moderate knee osteoarthritis, focal cartilage defects, and early-stage osteonecrosis (often paired with core decompression). MSCs are also studied for partial meniscus tears, partial ligament injuries, subchondral bone marrow lesions, and synovitis. They act primarily via paracrine anti-inflammatory and trophic signalling rather than direct tissue differentiation. MSCs are not indicated for active infection, severe malalignment, end-stage osteoarthritis, large structural defects, or full ligament ruptures. Evidence quality varies, and long-term durability is still being investigated.