Osteoarthritic knee: Advances in Epidemiology, Emerging Etiopathologies and Adipose-Derived Stem Cells-based Therapies.

Knee osteoarthritis (KOA) is a degenerative disorder that affects the joint in a non-uniform and focal manner. It is characterized by the loss of hyaline articular cartilage, along with bony remodeling, capsular stretching, and weakness of periarticular muscles. It could be ascribed to etiological factors that are modifiable (obesity, joint injury, occupational hazards, physical inactivity), non-modifiable (age, female gender, and genetic predisposition, racial/ethnic differences), or emerging, such as high blood pressure, vitamin D deficiency, and metabolic syndrome, which might contribute to KOA pathophysiology. KOA treatment is multimodal, and recent years have witnessed a shift from primarily pharmacologic, surgical to regenerative therapies ones, due to limited advantages of the former and evidence that advanced approaches are more likely to suppress pathological symptoms in the long term and to delay or prevent functional decline. Minimally invasive stem cell-based alternatives such as adipose-derived stem cells (ADSCs) are being explored owing to their differentiation potential towards chondro-, osteo-, and adipogenic lineages for osteochondral reparative regeneration. ADSC-derived extracellular vesicles, particularly exosomes (ADSC-exo), are gaining prominence in the treatment of KOA due to their unique regenerative and anti-inflammatory properties. These exosomes offer several advantages compared to cellular interventions, being a cell-free therapeutic strategy, low immunogenicity, and potential to deliver bioactive molecules, promote anti-inflammatory effects, and cartilage repair and regeneration. ADSC-exo expresses miRNA and improved safety by regulating various pathways such as PI3K/AKT/mTOR signaling or Wnt/β-catenin signalling. Combinatorial approaches have also been applied with ADSCs, such as platelet-rich plasma, shockwave therapy, xanthan gum, hyperbaric oxygenation, and nanoparticles, which have shown significant improvements in alleviating KOA. Based on the above evidence, we have reviewed the advances in epidemiology, emerging etiopathologies, and ADSCs-based revitalization strategies for the osteoarthritic knee joint.