Dental pulp stem cell-derived exosomes alleviate cerebral ischaemia-reperfusion injury through suppressing inflammatory response

Abstract

Objectives: The study aimed to determine whether dental pulp stem cell-derived exosomes (DPSC-Exos) exert protective effects against cerebral ischaemia-reperfusion (I/R) injury and explore its underlying mechanism. Materials and Methods: Exosomes were isolated from the culture medium of human DPSC. Adult male C57BL/6 mice were subjected to 2 hours transient middle cerebral artery occlusion (tMCAO) injury followed by 2 hours reperfusion, after which singular injection of DPSC-Exos via tail vein was administrated. Brain oedema, cerebral infarction and neurological impairment were measured on day 7 after exosomes injection. Then, oxygen-glucose deprivation–reperfusion (OGD/R) induced BV2 cells were studied to analyse the therapeutic effects of DPSC-Exos on I/R injury in vitro. Protein levels of TLR4, MyD88, NF-κB p65, HMGB1, IL-6, IL-1β and TNF-α were determined by western blot or enzyme-linked immunosorbent assay. The cytoplasmic translocation of HMGB1 was detected by immunofluorescence staining. Results: DPSC-Exos alleviated brain oedema, cerebral infarction and neurological impairment in I/R mice. DPSC-Exos inhibited the I/R-mediated expression of TLR4, MyD88 and NF-κB significantly. DPSC-Exos also reduced the protein expression of IL-6, IL-1β and TNF-α compared with those of the control both in vitro and in vivo. Meanwhile, DPSC-Exos markedly decreased the HMGB1 cytoplasmic translocation induced by I/R damage. Conclusions: DPSC-Exos can ameliorate I/R-induced cerebral injury in mice. Its anti-inflammatory mechanism might be related with the inhibition of the HMGB1/TLR4/MyD88/NF-κB pathway.