Work

Engineered MSC Aggregates with E/N‐Cadherin and IL‐6 Preconditioning for the Treatment of Systemic Sclerosis

Year: 2025

Type: article

Abstract: Umbilical cord‐derived mesenchymal stromal cells (MSCs) transplantation is a promising therapy for systemic sclerosis (SSc) because of their distinctive antifibrotic and immunomodulatory properties. To enhance the effects of MSCs transplantation, novel engineered MSC aggregates preconditioned with human E/N‐cadherin fusion protein (hE/N‐cad‐Fc) and interleukin‐6 (IL‐6) for SSc treatment are fabricated and named 3D‐Cad/IL6‐MSCs. These novel‐engineered MSC aggregates possess tighter cellular cohesion and exhibit enhanced antiapoptotic, immunosuppressive, and proangiogenic capabilities according to transcriptomic analyses. Moreover, 3D‐Cad/IL6‐MSCs have improved immunoregulatory effects on peripheral blood mononuclear cells (PBMCs), CD4+ T cells, and CD8+ T cells in vitro because of the synergistic preconditioning from IL‐6 and bioactive hE/N‐cad‐Fc. Upon intravenous injection, 3D‐Cad/IL6‐MSCs significantly mitigate skin and lung fibrosis and prolong the retention duration in bleomycin (BLM)‐induced SSc mouse model. In detail, they suppress excessive infiltration of macrophages and T cells in the injured skin and lungs and reestablish the immune equilibrium of circulating CD4+ T‐cell subsets in vivo. These results suggest that 3D‐Cad/IL6‐MSCs are ideal candidates for SSc therapy and optimize the clinical utilization of MSCs.

Source: Advanced Healthcare Materials

DOI: 10.1002/adhm.202500663