Gemodificeerde regulatoire T-lymfocyten bevorderen herstel van het geïnfarceerde hart

BACKGROUND:Myocardial infarction (MI) initiates a dysregulated healing process characterized by excessive fibrosis and unresolved inflammation, resulting in suboptimal cardiac repair in clinical settings. Regulatory T lymphocytes (Tregs) naturally orchestrate cardiac repair after MI, but their therapeutic potential is limited by inefficient homing to ischemic myocardium. We hypothesize that FAP (fibroblast activation protein)–specific CAR (chimeric antigen receptor) engineering overcomes this barrier by enabling precise delivery of Tregs to FAP⁺-enriched infarct zones, thereby focally amplifying reparative activity within injured myocardium.METHODS:In murine MI and ischemia–reperfusion models, C57BL/6J mice were injected with lentivirus-engineered FAP CAR Tregs (FCTRs) or mock Tregs derived from wild-type, IL-10 (interleukin-10) knockout (IL-10−/−) or Areg (amphiregulin) knockout (Areg−/−) donors after infarction. The cardiac outcomes and underlying mechanisms mediated by FCTRs were th