Mesenchymal Stem Cell Therapy for Knee Osteoarthritis

Osteoarthritis of the knee is characterised by progressive loss of articular cartilage, subchondral bone remodelling and low‐grade synovial inflammation, leading to pain and functional impairment. Conventional management focuses on symptom relief through analgesia, physiotherapy and, ultimately, joint replacement. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality owing to their capacity for multilineage differentiation, trophic support of native tissues and immunomodulatory activity. When delivered into the joint space by intra-articular injection, MSCs can engraft transiently, secrete anti-inflammatory and chondroprotective factors, and recruit endogenous repair mechanisms. Sources of MSCs include bone marrow, adipose tissue, umbilical cord and Wharton’s jelly, each with distinct proliferative and secretory profiles. Key challenges remain in defining optimal cell dose, choice of allogeneic versus autologous origin, methods of cell expansion or priming to enhance efficacy, and selection of patient subgroups most likely to benefit. Early-phase clinical trials and preclinical models have demonstrated safety, dose-dependent improvements in pain and function, and evidence of cartilage preservation or regeneration on imaging, but standardised protocols and larger controlled studies are required before routine implementation.

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Mesenchymal Stem Cell Therapy for Knee Osteoarthritis publication trend

The graph below shows the total number of articles in mesenchymal stem cell therapy for knee osteoarthritis across all publications each year (not limited to Nature Index journals).

Technical terms

Mesenchymal stem cells (MSCs): Multipotent stromal cells capable of differentiating into bone, cartilage and fat lineages, and of secreting bioactive molecules that modulate inflammation and tissue repair.

Intra-articular injection: Direct delivery of cells or therapeutic agents into the joint cavity to achieve localised effects.

Paracrine signalling: Local cell–cell communication mediated by the secretion of soluble factors that influence neighbouring cells.

Immunomodulation: The regulation or alteration of immune responses, often to mitigate inflammation.

Senescent chondrocytes: Cartilage cells that have ceased proliferation and secrete proinflammatory factors, contributing to tissue degeneration.

Allogeneic vs. Autologous: Allogeneic MSCs are derived from a donor, whereas autologous MSCs originate from the patient receiving the therapy.

References

1. Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success. Cellular & Molecular Immunology (2023).
2. Insulin-Like Growth Factor 2 Secreted from Mesenchymal Stem Cells with High Glutathione Levels Alleviates Osteoarthritis via Paracrine Rejuvenation of Senescent Chondrocytes. Biomaterials Research (2025).
3. A Phase I Dose-Escalation Clinical Trial to Assess the Safety and Efficacy of Umbilical Cord-Derived Mesenchymal Stromal Cells in Knee Osteoarthritis. Stem Cells Translational Medicine (2024).