Endothelial nitric oxide synthase-engineered mesenchymal stromal cells induce anti-inflammation in experimental immune models.

Abstract

Mesenchymal stromal cells (MSCs) remain an area of interest in the field of regenerative medicine. Although there is clear evidence of safety, a lack of substantial efficacy has led to many MSC-based clinical trials to stall in phase 1. Therefore, potentiating MSCs with biologically relevant messenger RNA (mRNA) transcripts presents a relatively safe and efficient way to increase functionality. In this study, human bone marrow-derived MSCs were transfected with endothelial nitric oxide synthase (eNOS) mRNA and evaluated for transfection efficiency and immunosuppressive ability. To assess MSC-eNOS functionality, T-cell proliferation assays and mouse models of experimental autoimmune encephalomyelitis and graft-versus-host disease were used. The authors found that MSC-eNOS retained MSC characteristics and exhibited significantly enhanced immunosuppressive effects compared with naive MSCs in both in vitro and in vivo models. It is feasible to pursue eNOS mRNA transfection to potentiate the immunomodulatory capacity of MSCs for clinical applications in the future.