Controversies in regenerative medicine: should knee joint osteoarthritis be treated with mesenchymal stromal cells?

Knee joint osteoarthritis is a complex immunological and degenerative disease. Current treatment strategies fail to alter its progression. Mesenchymal stromal cell (MSC) therapy for osteoarthritis has been object of research for more than 30 years. The aim of MSC therapy is intended to be holistic, with regeneration of all affected knee joint structures. The paracrine effect of the MSC secretome has been shown to be central for the regenerative capacity of MSCs. Activation of local knee-joint-specific MSCs leads to an immunomodulatory, anti-catabolic, anti-apoptotic and chondrogenic stimulus. Preclinical models have demonstrated the symptom-and disease-modifying effects of MSC therapy. At the bedside, there is evidence that autologous and allogeneic MSC therapy shows significant improvement in symptom-modifying and functional outcome. Despite this, a variety of contradictory clinical outcomes are available in the literature. The effectiveness of MSC therapy is still unclear, although there have been promising results. Regarding the diversity of cell sources, isolation, culture protocols and other factors, a comparison of different studies is difficult. Clinical translation of disease-modifying effects has not yet been shown. This narrative review presents a controversial overview of the current preclinical and clinical studies on MSC therapy in knee joint osteoarthritis.