iPSC-derived MSCs alleviate arthritis in collagen-induced arthritis mice by reducing synovial CD86h iIL1βhi macrophage

Background: Joint bone destruction in rheumatoid arthritis (RA) leads to poor prognosis, with current treatments mainly targeting inflammation and limited focus on bone damage. Mesenchymal stem cells (MSCs) offer anti-inflammatory and bone repair properties, but their clinical application is hindered by cellular heterogeneity. Induced pluripotent stem cell–derived mesenchymal stem cells (iMSCs) present a promising alternative due to their lower heterogeneity and replicative senescence, although their potential in RA treatment remains underexplored. Methods: iMSCs were injected intraarticularly in a collagen-induced arthritis (CIA) model. Treatment outcomes, including plantar swelling, joint score, histological and immunohistochemical staining, microCT imaging, and bone loss, were assessed. Single-cell RNA sequencing was employed to study iMSCs’ effects on synovial macrophage subsets. Results: In vivo, iMSCs significantly reduced systemic inflammation and joint bone damage. Analysis of macrophage subpopulations revealed that iMSCs shifted macrophages from a pro-inflammatory CD86hiIL1βhi cluster to an anti-inflammatory CD86hiIL1βlo cluster, leading to reduced inflammation and bone resorption. Conclusions: iMSCs effectively alleviate inflammation and bone damage in CIA by modulating macrophage phenotypes, demonstrating potential for RA therapy.