The reduction in immunogenicity of neurotrophin overexpressing stem cells after intra-striatal transplantation by encapsulation in an in situ gelling collagen hydrogel.
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.
Pharmacology & Therapeutics, National University of Ireland, Galway, Ireland; NCBES Galway Neuroscience Centre, National University of Ireland, Galway, Ireland.
Deirdre B
DB
Hoban
Ben
B
Newland
Teresa C
TC
Moloney
Linda
L
Howard
Abhay
A
Pandit
Eilís
E
Dowd
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001921:Brain / Q000276:immunology / Q000601:surgery*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000737:chemistry*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D006789:Host vs Graft Reaction; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054457:Tissue Scaffolds / Q000737:chemistry*; D015854:Up-Regulation
D001672:Biocompatible Materials; D024042:Collagen Type I; D051100:Glial Cell Line-Derived Neurotrophic Factor; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
Biomaterials; Cell transplantation; Glial cell line-derived neurotrophic factor (GDNF); Host response; Hydrogel; Neurodegenerative disease