Intravenous infusion of human bone marrow mesenchymal stromal cells promotes functional recovery and neuroplasticity after ischemic stroke in mice.
Eliana SammaliClaudia AliaGloria VeglianteValentina ColomboNadia GiordanoFrancesca PischiuttaGiorgio B BoncoraglioMario BarilaniLorenza LazzariMatteo CaleoMaria-Grazia De SimoniGiuseppe GaipaGiuseppe CiterioElisa R ZanierPublished in: Scientific reports (2017)
Transplantation of human bone marrow mesenchymal stromal cells (hBM-MSC) promotes functional recovery after stroke in animal models, but the mechanisms underlying these effects remain incompletely understood. We tested the efficacy of Good Manufacturing Practices (GMP) compliant hBM-MSC, injected intravenously 3.5 hours after injury in mice subjected to transient middle cerebral artery occlusion (tMCAo). We addressed whether hBM-MSC are efficacious and if this efficacy is associated with cortical circuit reorganization using neuroanatomical analysis of GABAergic neurons (parvalbumin; PV-positive cells) and perineuronal nets (PNN), a specialized extracellular matrix structure which acts as an inhibitor of neural plasticity. tMCAo mice receiving hBM-MSC, showed early and lasting improvement of sensorimotor and cognitive functions compared to control tMCAo mice. Furthermore, 5 weeks post-tMCAo, hBM-MSC induced a significant rescue of ipsilateral cortical neurons; an increased proportion of PV-positive neurons in the perilesional cortex, suggesting GABAergic interneurons preservation; and a lower percentage of PV-positive cells surrounded by PNN, indicating an enhanced plastic potential of the perilesional cortex. These results show that hBM-MSC improve functional recovery and stimulate neuroprotection after stroke. Moreover, the downregulation of "plasticity brakes" such as PNN suggests that hBM-MSC treatment stimulates plasticity and formation of new connections in the perilesional cortex.
Keyphrases
- bone marrow
- high fat diet induced
- extracellular matrix
- induced apoptosis
- middle cerebral artery
- endothelial cells
- functional connectivity
- mesenchymal stem cells
- primary care
- cell cycle arrest
- healthcare
- signaling pathway
- cell proliferation
- insulin resistance
- wild type
- brain injury
- cerebral ischemia
- pluripotent stem cells
- endoplasmic reticulum stress
- palliative care
- escherichia coli
- risk assessment
- cell death
- biofilm formation
- blood brain barrier
- adipose tissue
- gestational age
- preterm birth