Editors' ChoiceStem Cells

Breaking up forces stem cells to come together

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Science Translational Medicine  26 Aug 2020:
Vol. 12, Issue 558, eabd6007
DOI: 10.1126/scitranslmed.abd6007

Abstract

Microfracture surgery followed by local delivery of therapy induces stem cells to rebuild cartilage in osteoarthritis.

Osteoarthritis (OA) is a common disease among the elderly and results in degeneration of articular cartilage. A popular technique to regenerate cartilage is microfracture surgery, which punctures chondral bone to access the underlying marrow and induces a hematoma that is subsequently resorbed and replaced with fibrous tissue. This surgery and generation of fibrous tissue has been shown to provide some relief of OA symptoms. How skeletal stem cells (SSCs) contribute to regeneration of cartilage after microfracture surgery and in OA was unknown.

Murphy et al. first determined that SSCs are reduced with age, but still present in mouse and human. Further, these SSCs clonally expand after microfracture surgery at the injured joint. Microfracture induced an SSC phenotype that mimicked those from juvenile mice, displaying strong proliferative and chondrogenic potential. To further guide the SSCs toward a chondrogenic fate, the authors codelivered bone morphogenetic protein 2 (BMP2) and a soluble vascular endothelial growth factor inhibitor (sVEGFr1) after microfracture surgery in mice and observed mechanically robust cartilage formation. A reduction of SSCs also occurred in humans with age, but SSCs could still regenerate cartilage in a similar manner as adult mouse SSCs after microfracture surgery and codelivery of BMP2 and sVEGFr1.

Additional studies are needed to determine if OA pathology can be reversed in geriatric animals. It is also unclear how heterogeneous the population of SSCs is and whether there might be subsets of stem cells that display stronger regenerative potential than others. Integrating these results demonstrates a novel strategy for treatment of OA by priming stem cells to promote regeneration.

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