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The reduction in immunogenicity of neurotrophin overexpressing stem cells after intra-striatal transplantation by encapsulation in an in situ gelling collagen hydrogel
The reduction in immunogenicity of neurotrophin overexpressing stem cells after intra-striatal transplantation by encapsulation in an in situ gelling collagen hydrogel
- Source :
- Biomaterials. 34(37)
- Publication Year :
- 2013
-
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.
- Subjects :
- Male
Materials science
Biophysics
Bioengineering
Biocompatible Materials
Mesenchymal Stem Cell Transplantation
Collagen Type I
Hydrogel, Polyethylene Glycol Dimethacrylate
Biomaterials
Extracellular matrix
Rats, Sprague-Dawley
Neurotrophic factors
medicine
Glial cell line-derived neurotrophic factor
Animals
Humans
Glial Cell Line-Derived Neurotrophic Factor
Cells, Cultured
biology
Tissue Scaffolds
Mesenchymal stem cell
Brain
Mesenchymal Stem Cells
Cell biology
Rats
Up-Regulation
Transplantation
medicine.anatomical_structure
nervous system
Mechanics of Materials
Host vs Graft Reaction
Ceramics and Composites
biology.protein
Stem cell
Type I collagen
Biomedical engineering
Astrocyte
Subjects
Details
- ISSN :
- 18785905
- Volume :
- 34
- Issue :
- 37
- Database :
- OpenAIRE
- Journal :
- Biomaterials
- Accession number :
- edsair.doi.dedup.....3c1ff035052e7fa09131b58834c03f35