Mesenchymal stromal cells and polymeric vectors for tissue engineering of the central nervous system
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Auteurs : Gaëtan Delcroix [France]Source :
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Abstract
Mesenchymal stromal cells (MSCs) have several advantages for brain cell therapy. We first demonstrated that MSCs do not migrate in healthy rat brains whereas they were attracted by a lesion located far from their implantation site. However, we also confirmed that the poor cell survival and neuronal differentiation are the major obstacles encountered for brain cell therapy. Thus, we then focused on enhancing the neuronal differentiation potential of MSCs before transplantation, using an epidermal growth factor-basic fibroblast growth factor (EGF-bFGF) pre-treatment in vitro. Finally, we associated MSCs to polymeric vectors, the pharmacologically active microcarriers (PAMs), to increase cell survival and neuronal differentiation, and thereby favouring MSC tissue regeneration potential after transplantation. These PLGA microspheres were coated with a biomimetic surface of laminin, after demonstrating the benefits of this molecule on the neuronal differentiation potential of MSCs in vitro. After attachment of MSCs on their surface, neurotrophin releasing, laminin-coated PAMs have been evaluated in a rat model of Parkinson's disease. A significant functional recovery was observed compared to cells grafted without PAMs. This strategy is the first to give the proof of concept for the use of adult stem cells combined to bioactive polymeric vectors to protect the central nervous system in the context of Parkinson's disease.
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We first demonstrated that MSCs do not migrate in healthy rat brains whereas they were attracted by a lesion located far from their implantation site. However, we also confirmed that the poor cell survival and neuronal differentiation are the major obstacles encountered for brain cell therapy. Thus, we then focused on enhancing the neuronal differentiation potential of MSCs before transplantation, using an epidermal growth factor-basic fibroblast growth factor (EGF-bFGF) pre-treatment in vitro. Finally, we associated MSCs to polymeric vectors, the pharmacologically active microcarriers (PAMs), to increase cell survival and neuronal differentiation, and thereby favouring MSC tissue regeneration potential after transplantation. These PLGA microspheres were coated with a biomimetic surface of laminin, after demonstrating the benefits of this molecule on the neuronal differentiation potential of MSCs in vitro. After attachment of MSCs on their surface, neurotrophin releasing, laminin-coated PAMs have been evaluated in a rat model of Parkinson's disease. A significant functional recovery was observed compared to cells grafted without PAMs. This strategy is the first to give the proof of concept for the use of adult stem cells combined to bioactive polymeric vectors to protect the central nervous system in the context of Parkinson's disease.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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