Enucleated mesenchymal stem cell carrier enhance therapeutic effect on rheumatoid arthritis rats through regulation of joint synovium (PRJCA031415)
Mesenchymal stem cells (MSCs) offer a promising rheumatoid arthritis (RA) therapy, but intravenous MSCs initially trap in lung capillaries, reducing therapeutic efficacy and risking complications, with safety concerns including unwanted differentiation and malignancy. In this study, we generated enucleated human umbilical cord-derived MSCs overexpressing CCR2 and IFN-? (En-MSCsC/I), which retained essential organelles and exhibited immune regulatory, paracrine, and homing capabilities. Intravenous administration of either MSCs or En-MSCsC/I alleviated synovitis in RA rat model by modulating immune and inflammatory processes of fibroblast-like synoviocytes and myeloid cells, as revealed by single-cell RNA sequencing analysis. En-MSCsC/I promoted the secretion of factors such as SEMA3E, which might play an important role in synovitis amelioration and cartilage regeneration. Compared to MSCs, En-MSCsC/I demonstrated superior migration to injured joints and unique regulatory signature for cartilage regeneration. Our study suggests that En-MSCsC/I may offer improved therapeutic effects for RA-related cartilage damage while maintaining favorable safety profiles.