Small extracellular vesicles released by infused mesenchymal stromal cells target M macrophages and promote TGF-β upregulation, microvascular stabilization and functional recovery in a rodent model of severe spinal cord injury

The study investigates how mesenchymal stem cells (MSCs) improve recovery after spinal cord injury (SCI). It focuses on small extracellular vesicles (sEVs) released by MSCs, which are taken up by immune cells called M2 macrophages. The research found that these sEVs, when given in multiple smaller doses, mimic the beneficial effects of MSCs themselves. These effects include promoting tissue repair and reducing inflammation at the injury site. This suggests that MSCs might work by releasing sEVs that signal to M2 macrophages, leading to improved blood vessel stability and functional recovery after SCI.

• 1
  sEVs released by MSCs in vivo traffic to the injury site and are specifically associated with M2 macrophages.
• 2
  Fractionated dosing of MSC-sEVs over 3 days (F-sEVs) was required to achieve similar therapeutic effects as a single MSC injection.
• 3
  Infusion of F-sEVs increased expression of M2 macrophage markers, upregulated TGF-β, TGF-β receptors, and tight junction proteins, and reduced BSCB permeability.