Osteoarthritis

Osteoarthritis is the most common joint disease, affecting over 500 million people worldwide. The knee, hip, and hand joints are most often involved. The disease is driven by chondrocyte loss, destruction of cartilage collagen matrix and proteoglycans, osteophyte formation, and synovial membrane inflammation. Clinical features include pain on movement, stiffness, limited mobility, and progressive joint deformation with functional loss. Standard therapy — NSAIDs, chondroprotectors, physiotherapy, intra-articular injections of hyaluronic acid and corticosteroids — provides only temporary effect and does not halt progression. In end-stage disease the only effective option is joint replacement. Cell therapy is considered a means of slowing progression in early and middle stages, postponing or avoiding surgery.

According to the Global Burden of Disease, osteoarthritis ranks among the top ten causes of adult disability. Prevalence rises with age — radiographically confirmed OA of at least one joint affects 50% of people over 65, and 25% have clinically significant pain and functional limitation. Knee OA (gonarthrosis) affects ~10% of adults over 55 years; hip OA — ~5%; hand OA — ~10%, particularly in postmenopausal women. The principal modifiable risk factors are excess weight and obesity (BMI >30 raises knee OA risk fourfold), prior joint injury (ACL tear, meniscectomy, articular surface fractures), and repetitive mechanical loading in occupations (miners, tilers, assembly-line workers). Non-modifiable factors include age, female sex after menopause, hereditary predisposition, and varus or valgus limb alignment. Metabolic comorbidities (diabetes, hypertension, dyslipidaemia) raise risk through systemic inflammatory background.

Modern OA neurobiology refutes the simplistic "age-related cartilage wear" model. OA is an active inflammatory and metabolic process. Chondrocytes normally maintain a balance of matrix synthesis and degradation; in OA they switch to a catabolic phenotype, upregulating matrix metalloproteinases MMP-1, MMP-3, MMP-13 and aggrecanases ADAMTS-4 and ADAMTS-5, which degrade type II collagen and aggrecan — key matrix components. Concurrently, the synovial membrane develops chronic inflammation with IL-1β, TNF-α, IL-6, MCP-1 production; this "low-grade synovitis" is no less significant than cartilage loss. Subchondral bone undergoes reactive remodelling — bone cysts, marginal osteophytes, and on MRI "bone marrow oedema" lesions correlating with pain. Pain in OA is multifactorial: synovitis, bone marrow lesions, peripheral and central nociceptive sensitisation. This explains why radiographic stage and pain intensity often do not correlate.

Conservative OA management (ACR 2019, EULAR 2023, OARSI 2019) is built on a core of patient education + dosed physical activity + weight control. Weight loss of 5–10% reduces knee pain by approximately 50% — an effect comparable to any pharmacotherapy. Exercise programmes include strengthening (especially quadriceps in gonarthrosis), aerobic activity, and neuromuscular stability training. Topical NSAIDs are preferred in knee and hand OA; oral NSAIDs — short courses with gastric and cardiovascular protection. Intra-articular corticosteroids provide short-term relief, but repeated administration may accelerate cartilage degradation. Hyaluronic acid is contested: recent guidelines have weakened the recommendation owing to ambiguous RCT data. Platelet-rich plasma (PRP) shows encouraging results in systematic reviews. Surgical options: arthroscopic debridement is NOT recommended for isolated OA (RCTs negative); osteotomy is effective in selected unicompartmental disease with axial deformity; total joint arthroplasty is the gold standard for end-stage disease but has limited prosthesis lifespan (15–20 years) and complication risk.

Mesenchymal cell therapy targets pathogenic mechanisms inaccessible to NSAIDs and chondroprotectors. UC-MSCs delivered intra-articularly reduce concentrations of pro-inflammatory cytokines and MMPs in synovial fluid, secrete paracrine factors supporting surviving chondrocytes (TGF-β3, FGF-2, IGF-1), can differentiate into chondrocytes producing new cartilage matrix, activate endogenous chondral progenitors, and attenuate subchondral remodelling. The double-blind RCT of intra-articular UC-MSC in moderate-to-severe knee OA with synovitis (BMC Musculoskeletal Disorders, 2025) showed significant WOMAC reduction at 6 months versus control. The 2025 RCT meta-analysis (Stem Cell Research & Therapy) confirmed reproducible WOMAC improvement at 6 and 12 months without increased adverse events. Outcomes are comparable between UC-MSCs and adipose-derived MSCs, allowing use of an allogeneic product without autologous fat harvesting.

The Hanshi United programme for OA comprises three intra-articular UC-MSC injections under ultrasound guidance at 15–30 day intervals. In polyarticular involvement (e.g., knees + hips + hands simultaneously), a combined protocol is used: an intravenous infusion for systemic anti-inflammatory effect plus local injections in the most symptomatic joints. After each procedure — sparing regimen for 48–72 hours without intensive load, then active physiotherapy and therapeutic exercise. NSAIDs are temporarily withdrawn 5–7 days before and after administration to avoid suppressing local prostaglandin signalling cascades important to the regenerative response. Optimal candidates are stages Kellgren-Lawrence I–II (minimal and moderate changes), occasionally stage III with preserved range of motion. At stage IV (severe deformity, bone-on-bone contact, varus/valgus >10°), cell therapy is considered only as palliative — the principal route in this group remains arthroplasty.