Intravenous infusion of human bone marrow mesenchymal stromal cells promotes functional recovery and neuroplasticity after ischemic stroke in mice

Abstract 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, in...

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Autores principales:	Eliana Sammali, Claudia Alia, Gloria Vegliante, Valentina Colombo, Nadia Giordano, Francesca Pischiutta, Giorgio B. Boncoraglio, Mario Barilani, Lorenza Lazzari, Matteo Caleo, Maria-Grazia De Simoni, Giuseppe Gaipa, Giuseppe Citerio, Elisa R. Zanier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a8c9b8a3d0b47f0851e220fca0f3975
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spelling	oai:doaj.org-article:4a8c9b8a3d0b47f0851e220fca0f39752021-12-02T11:50:55ZIntravenous infusion of human bone marrow mesenchymal stromal cells promotes functional recovery and neuroplasticity after ischemic stroke in mice10.1038/s41598-017-07274-w2045-2322https://doaj.org/article/4a8c9b8a3d0b47f0851e220fca0f39752017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07274-whttps://doaj.org/toc/2045-2322Abstract 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.Eliana SammaliClaudia AliaGloria VeglianteValentina ColomboNadia GiordanoFrancesca PischiuttaGiorgio B. BoncoraglioMario BarilaniLorenza LazzariMatteo CaleoMaria-Grazia De SimoniGiuseppe GaipaGiuseppe CiterioElisa R. ZanierNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eliana Sammali Claudia Alia Gloria Vegliante Valentina Colombo Nadia Giordano Francesca Pischiutta Giorgio B. Boncoraglio Mario Barilani Lorenza Lazzari Matteo Caleo Maria-Grazia De Simoni Giuseppe Gaipa Giuseppe Citerio Elisa R. Zanier Intravenous infusion of human bone marrow mesenchymal stromal cells promotes functional recovery and neuroplasticity after ischemic stroke in mice
description	Abstract 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.
format	article
author	Eliana Sammali Claudia Alia Gloria Vegliante Valentina Colombo Nadia Giordano Francesca Pischiutta Giorgio B. Boncoraglio Mario Barilani Lorenza Lazzari Matteo Caleo Maria-Grazia De Simoni Giuseppe Gaipa Giuseppe Citerio Elisa R. Zanier
author_facet	Eliana Sammali Claudia Alia Gloria Vegliante Valentina Colombo Nadia Giordano Francesca Pischiutta Giorgio B. Boncoraglio Mario Barilani Lorenza Lazzari Matteo Caleo Maria-Grazia De Simoni Giuseppe Gaipa Giuseppe Citerio Elisa R. Zanier
author_sort	Eliana Sammali
title	Intravenous infusion of human bone marrow mesenchymal stromal cells promotes functional recovery and neuroplasticity after ischemic stroke in mice
title_short	Intravenous infusion of human bone marrow mesenchymal stromal cells promotes functional recovery and neuroplasticity after ischemic stroke in mice
title_full	Intravenous infusion of human bone marrow mesenchymal stromal cells promotes functional recovery and neuroplasticity after ischemic stroke in mice
title_fullStr	Intravenous infusion of human bone marrow mesenchymal stromal cells promotes functional recovery and neuroplasticity after ischemic stroke in mice
title_full_unstemmed	Intravenous infusion of human bone marrow mesenchymal stromal cells promotes functional recovery and neuroplasticity after ischemic stroke in mice
title_sort	intravenous infusion of human bone marrow mesenchymal stromal cells promotes functional recovery and neuroplasticity after ischemic stroke in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4a8c9b8a3d0b47f0851e220fca0f3975
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Intravenous infusion of human bone marrow mesenchymal stromal cells promotes functional recovery and neuroplasticity after ischemic stroke in mice

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