Efficient Treatment of Pulpitis via Transplantation of Human Pluripotent Stem Cell-Derived Pericytes Partially through

Dental pulp pericytes are reported to have the capacity to generate odontoblasts and express multiple cytokines and chemokines that regulate the local immune microenvironment, thus participating in the repair of dental pulp injury in vivo. However, it has not yet been reported whether the transplantation of exogenous pericytes can effectively treat pulpitis, and the underlying molecular mechanism remains unknown. In this study, using a lineage-tracing mouse model, we showed that most dental pulp pericytes are derived from cranial neural crest. Then, we demonstrated that the ablation of pericytes could induce a pulpitis-like phenotype in uninfected dental pulp in mice, and we showed that the significant loss of pericytes occurs during pupal inflammation, implying that the transplantation of pericytes may help to restore dental pulp homeostasis during pulpitis. Subsequently, we successfully generated pericytes with immunomodulatory activity from human pluripotent stem cells through the intermediate stage of the cranial neural crest with a high level of efficiency. Most strikingly, for the first time we showed that, compared with the untreated pulpitis group, the transplantation of hPSC-derived pericytes could substantially inhibit vascular permeability (the extravascular deposition of fibrinogen, **