Identification of disease-stage therapeutic responses of mesenchymal stromal cells retrieved from murine osteoarthritic joints

• DOI: 10.3389/fcell.2025.1521437
• Publication Date: 2025-03-26T14:25:53Z
• Authors: Ana Ivanovska; Patrizio Mancuso; Amy Burke; Conor Hennessy; Swarna Raman; Claire Dooley; Steven McLoughlin; Georgina Shaw; Eka Mukeria; Jamie Reilly; Aisling O’Brien; Thomas Ritter; Aideen E. Ryan; Raj Kamath; Marc C. Levesque; Deborah Van Riet; Karen English; Ian Hawthorne; Brian Johnstone; Derek W. Morris; Frank Barry; J. Mary Murphy

Objective Osteoarthritis (OA) is a widespread and debilitating joint disease characterized by synovial inflammation, cartilage degeneration, chronic pain. Mesenchymal stromal cells (MSCs) have shown therapeutic efficacy for many diseases with strong inflammatory profile, including OA. However, the disease-specific mechanisms of action underpinning effects post-local MSC delivery remain unaddressed. In this study, we aimed to characterize disease-induced profile MSCs following exposure in vivo osteoarthritis environment. Methods Murine syngeneic GFP + bone marrow-derived (BM-MSCs) were delivered via intra-articular injection mouse collagenase-induced (CIOA) model (n = 8). BM-MSCs retrieved cell sorting on days 14 56, whole knee digestions. The expanded culture based their phenotype, immunomodulatory lymphocytes macrophages, transcriptomic profile. Results Retrieved (1.33%) had minimal lymphocyte proliferation but induced macrophage anti-inflammatory activity. Surviving activated various pathways, secretome impacting immune system regulation extracellular matrix organization, correlating stage. Data comparing profiles vitro- licensed suggested chondroprogenitor identified BRINP3 as novel factor function potential OA modulation. Conclusion beneficial could be attributed specific subset able resist micro-inflammatory milieu contribute healing suppression associated inflammation. Furthermore, data suggest paradigm environmentally guided plasticity upon local both early late