https://boa.unimib.it/retrieve/handle/10281/163867/233929/s41598-017-07274-w.pdf
Eliana Sammali
1,2
,
Claudia Alia 3,4 ,
Gloria Vegliante 1 ,
Valentina Colombo 5,6 ,
Nadia Giordano 3,4 ,
Francesca Pischiutta 1 ,
Giorgio B. Boncoraglio 2 ,
Mario Barilani 7 ,
Lorenza Lazzari 7 ,
Matteo Caleo 3 ,
Maria-Grazia De Simoni 1 ,
Giuseppe Gaipa 5,6 ,
Giuseppe Citerio 8,9 &
Elisa R. Zanier 1
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 down regulation of “plasticity brakes” such as PNN suggests that hBM-MSC treatment stimulates plasticity and formation of new connections in the perilesional cortex.
Claudia Alia 3,4 ,
Gloria Vegliante 1 ,
Valentina Colombo 5,6 ,
Nadia Giordano 3,4 ,
Francesca Pischiutta 1 ,
Giorgio B. Boncoraglio 2 ,
Mario Barilani 7 ,
Lorenza Lazzari 7 ,
Matteo Caleo 3 ,
Maria-Grazia De Simoni 1 ,
Giuseppe Gaipa 5,6 ,
Giuseppe Citerio 8,9 &
Elisa R. Zanier 1
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 down regulation of “plasticity brakes” such as PNN suggests that hBM-MSC treatment stimulates plasticity and formation of new connections in the perilesional cortex.
No comments:
Post a Comment