Exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation after traumatic brain injury
Liang Wen1, Ya-Dong Wang1, Dong-Feng Shen2
1The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Abstract:
Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair. However, the underlying molecular mechanism remains unclear. In this study, we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation. Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype, inhibited the expression of proinflammatory cytokines, and increased the expression of anti-inflammatory cytokines. Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury, inhibited neuroinflammation, and promoted the transformation of microglia to the anti-inflammatory phenotype. We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process. Finally, we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection. We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype. The interleukin 10/STAT3 pathway was activated during this process. These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway.
Insights
Bone marrow mesenchymal stem cell exosomes reduce neuroinflammation after traumatic brain injury by modulating microglial phenotypes. MicroRNA-181b plays a key role in this process via the IL-10/STAT3 pathway.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Cell Biology
Background:
- Exosomes from bone marrow mesenchymal stem cells (BMSCs) show potential in treating neuroinflammation and nerve injury.
- The precise molecular mechanisms underlying BMSC exosome efficacy in neuroinflammation remain largely unknown.
Purpose of the Study:
- To elucidate the mechanism by which BMSC-derived exosomes inhibit neuroinflammation and promote nerve repair.
- To investigate the role of microRNA-181b (miR181b) in the therapeutic effects of BMSC exosomes on traumatic brain injury (TBI).
Main Methods:
- In vitro co-culture of BMSCs and BV2 microglia to assess microglial polarization and cytokine expression.
- In vivo studies using mouse models of TBI treated with BMSC exosomes via tail vein injection.
- MicroRNA sequencing to identify key microRNAs involved in neuroinflammation.
- Lentiviral transfection to manipulate miR181b expression in TBI mouse models.
Main Results:
- BMSC exosomes promoted anti-inflammatory microglial polarization, reduced pro-inflammatory cytokines, and increased anti-inflammatory cytokines in vitro.
- Exosome treatment in vivo reduced apoptosis, inhibited neuroinflammation, and shifted microglia to an anti-inflammatory phenotype in TBI mice.
- miR181b was identified as a key player; its overexpression in TBI models reduced apoptosis and neuroinflammation, promoting anti-inflammatory microglial phenotypes.
- The interleukin-10/STAT3 pathway was activated by miR181b during the neuroprotective process.
Conclusions:
- BMSC-derived exosomes exert neuroprotective effects in TBI by inhibiting neuroinflammation and promoting nerve repair.
- MicroRNA-181b is a critical mediator of these effects, acting through the interleukin-10/STAT3 pathway.
- These findings highlight a novel therapeutic mechanism for BMSC exosomes in TBI treatment.
