Researchers Develop Novel Exosome-based Therapeutic Agent For Treating Traumatic Cns Injuries

Traumatic injuries of nan cardinal tense strategy (CNS)-such arsenic traumatic encephalon wounded (TBI) and traumatic spinal cord wounded (SCI)-are characterized by oxidative harm and neuroinflammation. Current curen relies chiefly connected supportive attraction and surgical intervention, pinch a deficiency of effective narcotics to straight target nan underlying damage.

For example, neural stem compartment (NSC)-based therapy has shown therapeutic potential, but pathological microenvironments negatively effect NSC endurance and directed differentiation, compromising therapeutic outcomes. Similarly, antioxidant curen has constricted occurrence because astir antioxidants don't efficiently transverse nan blood-brain obstruction (BBB).

Now, however, researchers from nan Institute of Process Engineering (IPE) of nan Chinese Academy of Sciences, successful practice pinch Shenzhen Second People's Hospital, person developed a caller exosome-based therapeutic supplier for treating traumatic CNS injuries. This curen tin alleviate neuronal apoptosis, reconstruct glial homeostasis, and remodel glia-neuron networks, offering potent therapeutic benefits successful murine (mouse) TBI and SCI models.

The study was published in Cell Reports Medicine.

Understanding that NSC therapy involves cell-to-cell connection via exosomes-nanosized vesicles secreted by cells, including NSCs-the researchers projected utilizing NSC-derived exosomes (NExo) to dainty CNS injury, since nan exosomes are unchangeable and stay medically progressive successful nan pathological microenvironment.

The researchers besides understood that exosome-based therapy needed to reside oxidative harm caused by reactive oxygen type (ROS) successful nan microenvironment.

Inspired by selenium's capacity to scavenge ROS, nan researchers developed an precocious NExo containing ultrasmall nano-selenium (~3.5 nm) via lipid-mediated nucleation (SeNExo).

Prof. MA Guanghui from IPE said that SeNExo penetrated nan BBB via nan APOE_LRP-1 relationship aft intravenous injection. Upon efficiently reaching nan lesion site, nan ultrasmall nano-selenium efficaciously scavenged ROS, while NExo promoted neuronal repair.

In a rodent TBI model, SeNExo reduced cerebral lesions and improved spatial learning and representation functions. Through proteomics, miRNA omics, and single-nucleus RNA sequencing, nan researchers demonstrated that SeNExo importantly downregulated nan look of genes related to oxidative accent and apoptosis successful neurons. In addition, SeNExo profoundly altered nan transcriptional programme of inflammatory responses, promoting glial cells toward homeostasis. Moreover, SeNExo enhanced neuron-glia ligand-receptor pairs progressive successful CNS improvement while suppressing those associated pinch inflammation and astrogliosis. In a rodent SCI model, SeNExo besides promoted locomotor recovery.

Both Prof. TAN Hui from Shenzhen Children's Hospital and LI Weiping from Shenzhen Second People's Hospital support nan conception that SeNExo is simply a caller and promising therapeutic supplier for treating traumatic CNS injury.

One adjacent reviewer from Cell Report Medicine said that nan study provides convincing grounds that SeNExo tin protect nan encephalon pursuing TBI and perchance SCI.

Prof. WEI Wei from IPE said that SeNExo offers fantabulous biocompatibility and stability. He besides noted that its potent therapeutic efficacy and information item its promising translational imaginable for processing clinically applicable CNS wounded treatments.