The reduction in immunogenicity of neurotrophin overexpressing stem cells after intra-striatal transplantation by encapsulation in an in situ gelling collagen hydrogel.
Biomaterials
; 34(37): 9420-9, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-24054846
ABSTRACT
Delivery of neurotrophic factors to the brain via genetically modified bone marrow-derived mesenchymal stem cells (MSCs) offers a promising neuroprotective strategy for neurodegenerative diseases. However, MSCs delivered to the CNS typically show poor survival post-transplantation, which is accompanied by microglial activation and astrocyte recruitment at the graft site. Recent studies have shown the potential of biomaterials to provide a supportive matrix for transplanted cells which may assist in the grafting process. In this study, an in situ gelling type I collagen hydrogel was evaluated as an intracerebral transplantation matrix for delivery of glial cell line-derived neurotrophic factor (GDNF)-overexpressing MSCs to the rat brain (GDNF-MSCs). In vitro analyses demonstrated that this collagen hydrogel did not affect the viability of the GDNF-MSCs nor did it prevent GDNF secretion into the surrounding medium. In vivo analyses also confirmed that the collagen hydrogel did not negatively impact on the survival of the cells and permitted GDNF secretion into the striatal parenchyma. Importantly, this study also revealed that transplanting GDNF-MSCs in a collagen hydrogel significantly diminished the host brain's response to the cells by reducing the recruitment of both microglia and astrocytes at the site of delivery. In conclusion, this hydrogel, which is composed of the natural extracellular matrix, collagen, was shown to be a well-tolerated cell delivery platform technology which could be functionalised to further aid cell support and graft integration.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Hidrogel de Polietilenoglicol-Dimetacrilato
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Colágeno Tipo I
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Transplante de Células-Tronco Mesenquimais
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Fator Neurotrófico Derivado de Linhagem de Célula Glial
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Alicerces Teciduais
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Células-Tronco Mesenquimais
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biomaterials
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Irlanda