BM-derived mesenchymal stem cell microvesicles protect enteric neural precursor cells and alleviate diabetes-associated enteric neuropathy - PubMed
2 months ago
- #Neuroscience
- #Gastroenterology
- #Neuronal stem cells
- BM-derived mesenchymal stem cell microvesicles (BMSC-MVs) protect enteric neural precursor cells (ENPCs) and alleviate diabetes-associated enteric neuropathy.
- Enteric nervous system (ENS) injury is a common diabetic complication with no effective cure beyond symptomatic management.
- ENPCs play a key role in maintaining neurogenesis and gliogenesis within the adult ENS.
- In diabetic patients and mouse models, gastrointestinal transit was delayed, ENS structure was impaired, and neurogenesis and gliogenesis from ENPCs were elevated but functionally insufficient.
- Transcriptomic profiling revealed activation of ER stress and the pro-apoptotic PERK branch of the unfolded protein response in ENPCs.
- BMSC-MVs homed to the colon, were internalized by ENPCs, and suppressed ER stress, enhancing functional neurogenesis and gliogenesis, restoring ENS structure, and improving gastrointestinal motility.
- Mechanistically, vinculin on BMSC-MVs bound talin-1 on ENPCs, activating the ERK pathway to suppress diabetic ER stress.
- BMSC-MVs are identified as a promising cell-free therapeutic strategy for diabetic ENS injury.