Nat Med. 2020 Oct;26(10):15831592 Abstract: https://pubmed.ncbi.nlm.nih.gov/32807933/
In brief: Improved treatments for osteoarthritis and other degenerative joint diseases are urgently needed. This study demonstrates, for the first time, that the synovial microenvironment can be modified to allow resident skeletal stem cells to form hyaline articular cartilage and thereby regenerate injured articular cartilage.
Comment: Murphy et al. investigated the ability of resident skeletal stem cell (SSC) populations to promote cartilage regeneration in relation to age. Age likely contributes to osteoarthritis, a degenerative joint disease that results in progressive destruction of articular cartilage, caused by a combination of multiple factors. This paper demonstrates that a progressive depletion of resident stem-cell pool and diminished chondrogenesis are associated with aging in mice and human joints, by using different βactin-Cre-ERT/Rainbow mouse models assessing changes in clonal skeletogenesis. Results were reproduced by human SSCs in a preclinical xenograft model.
Microfracture (MF) surgery is widely used to attempt to regenerate cartilage in OA. A fibrous cartilage is formed, providing relief to patients despite having reduced mechanical properties. The authors used MF surgery in a mouse model of OA and observed a localized expansion of SSCs in adult osteoarthritic mice joints and increased cartilage formation. To promote articular rather than fibrous cartilage formation, the authors used BMP2 localized co-delivery in a hydrogel, together with soluble VEGFR1, a VEGF receptor antagonist, in a model of meniscectomy-induced OA, and found that it overcomes the MS-activated SSC formation of fibrous cartilage and promote the differentiation of MF-activated SSCs toward hyaline cartilage.
In summary, this is one of the first studies to show that specific activation of resident skeletal stem cell population could be used for stable articular cartilage regeneration for localized treatment of articular cartilage injuries and osteoarthritis.