Mesenchymal stem cells for subchondral bone marrow lesions: From bench to bedside

Subchondral bone marrow lesions (BMLs) are areas of disease within subchondral bone that appear as T1 hypointense and T2 hyperintense ill-defined areas of bone marrow on magnetic resonance imaging. The most common bone marrow lesions include subchondral lesions related to osteoarthritis, osteochondral defects, and avascular necrosis. Emerging therapies include autologous biologic therapeutics, in particular mesenchymal stem cells (MSCs), to maintain and improve cartilage health; MSCs have become a potential treatment option for BMLs given the unmet need for disease modification. Active areas in the preclinical research of bone marrow lesions include the paracrine function of MSCs in pathways of angiogenesis and inflammation, and the use of bioactive scaffolds to optimize the environment for implanted MSCs by facilitating chondrogenesis and higher bone volumes. A review of the clinical data demonstrates improvements in pain and functional outcomes when patients with knee osteoarthritis were treated with MSCs, suggesting that BM-MSCs can be a safe and effective treatment for patients with painful knee osteoarthritis with or without bone marrow lesions. Preliminary data examining MSCs in osteochondral defects suggest they can be beneficial as a subchondral injection alone, or as a surgical augmentation. In patients with hip avascular necrosis, those with earlier stage disease have improved outcomes when core decompression is augmented with MSCs, whereas patients in later stages post-collapse have equivalent outcomes with or without MSC treatment. While the evidence for the use of MSCs in conditions with associated bone marrow lesions seems promising, there remains a need for continued investigation into this treatment as a viable treatment option.