Small extracellular vesicles released by infused mesenchymal stromal cells target M2 macrophages and promote TGF-β upregulation, microvascular stabilization and functional recovery in a rodent model of severe spinal cord injury.

ABSTRACT: Intravenous (IV) infusion of bone marrow-derived mesenchymal stem/stromal cells (MSCs) stabilizes the blood-spinal cord barrier (BSCB) and improves functional recovery in experimental models of spinal cord injury (SCI). Although IV delivered MSCs do not traffic to the injury site, IV delivered small extracellular vesicles (sEVs) derived from MSCs (MSC-sEVs) do and are taken up by a subset of M2 macrophages. To test whether sEVs released by MSCs are responsible for the therapeutic effects of MSCs, we tracked sEVs produced by IV delivered DiR-labelled MSCs (DiR-MSCs) after transplantation into SCI rats. We found that sEVs were released by MSCs in vivo, trafficked to the injury site, associated specifically with M2 macrophages and co-localized with exosome markers. Furthermore, while a single

SUBMITTER: Nakazaki M 

PROVIDER: S-EPMC8408371 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature