hUMSC-Exosomes suppress TREM1-p38 MAPK signaling via HMGB1-dependent mechanisms to reprogram microglial function and promote neuroprotection in ischemic stroke

Our findings delineate a novel HMGB1-TREM1-p38 MAPK axis through which hUMSC-Exos mitigate post-stroke neuroinflammation. By delivering HMGB1, hUMSC-Exos inhibit TREM1-dependent NF-κB/p38 activation, reprogram microglial function, and confer neuroprotection. Validated across in vivo, primary, and BV2 microglial models, and supported by multi-omics analyses, this study establishes hUMSC-Exos as a promising cell-free therapy targeting microglial reprogramming for ischemic stroke recovery.