Extracellular vesicle-mediated restraint of hepatic CD74-NF-κB repairs diabetic neuropathy.

Systemically delivered MSC-derived extracellular vesicles in diabetic mice predominantly accumulate in the liver and improve peripheral nerve structure and function, with benefits linked to hepatic CD74-NF-κB restraint.

• Why it matters: Diabetic peripheral neuropathy affects up to half of people with diabetes and has no disease-modifying therapy, leaving a gap in cross-organ mechanisms that could be targeted.
• What they did: The study profiled MSC-EV biodistribution and multiomic programs across diabetic models, establishing nerve repair in db/db mice and corroborating it in high-fat diet/streptozotocin- and methionine-choline-deficient mice.
• The result: EVs reduced circulating injury markers and spinal inflammation, and EV-encapsulated miR-24-3p repressed hepatic CD74, lowering MHC II/NF-κB activity in macrophages; hepatic CD74 overexpression worsened nerve injury, while NF-κB inhibition recapitulated EV benefits.

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