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.