Clonal articular cartilage progenitors outperform mesenchymal stromal cells in mitigating post-traumatic osteoarthritis.

OBJECTIVE

This study aimed to compare the functional, pathological, and immunomodulatory properties of articular chondroprogenitors (ACPs) with those of bone-marrow-derived mesenchymal stromal cells (MSCs) in preventing the progression of post-traumatic osteoarthritis (PTOA) after destabilization of the medial meniscus (DMM) injury in a mouse model.

METHOD: ACP and MSC were isolated from three horses and assessed for their immunomodulatory capacity in vitro. Aliquots of selected ACP clones and MSCs were injected intra-articularly into male mice 1-week post destabilization of the medial meniscus (DMM). The functional mobility of the mice before the injury and at weeks 2, 4, and 8 post-injury was assessed by two methods: ANY-maze™ voluntary mobility monitoring and DigiGait™ compulsory gait analysis. Upon euthanasia, joints were collected for histological scoring.

RESULTS

In vitro assessments demonstrated that ACPs and MSCs had anti-inflammatory properties: both treatments produced lower levels of pro-inflammatory cytokines, while only the ACPs produced more anti-inflammatory cytokines than controls. In vivo, both ACPs and MSCs lessened the effects of DMM on mobility. Histological scoring revealed significant reductions of PTOA in the medial compartment with ACPs relative to both MSCs and vehicle controls. Overall, ACPs effectively reduced PTOA progression to a greater extent than MSCs.

CONCLUSION

Our findings demonstrated that both equine ACP and MSC treatments provided symptom modification over vehicle controls in a short-term animal study. Notably, ACPs may be more efficacious than MSCs at reducing structural joint pathology.