Anti-inflammatory cytokine-eluting collagen hydrogel reduces the host immune response to dopaminergic cell transplants in a rat model of Parkinson’s disease

Author:

Cabré Sílvia123ORCID,Alamilla Verónica12,Moriarty Niamh14,Pandit Abhay2ORCID,Dowd Eilís1ORCID

Affiliation:

1. Pharmacology and Therapeutics and Galway Neuroscience Centre, National University of Ireland (NUI), Galway, Ireland

2. CÚRAM SFI Research Centre for Medical Devices, National University of Ireland (NUI), Galway, Ireland

3. Anatomy and Neuroscience and APC Microbiome Institute, University College Cork (UCC), Cork, Ireland

4. The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville 3052, Victoria, Australia

Abstract

Abstract In cell replacement approaches for Parkinson’s disease, the intracerebral implantation of dopamine neuron-rich grafts generates a neuroinflammatory response to the grafted cells that contributes to its varied outcome. Thus, the aim of the present study was to fabricate an anti-inflammatory cytokine-eluting collagen hydrogel capable of delivering interleukin (IL)-10 to the brain for reduction of the neuroinflammatory response to intracerebral cellular grafts. In vitro assessment revealed that cross-linker concentration affected the microstructure and gelation kinetics of the hydrogels and their IL-10 elution kinetics, but not their cytocompatibility or the functionality of the eluted IL-10. In vivo evaluation revealed that the hydrogels were capable of delivering and retaining IL-10 in the rat striatum, and reducing the neuroinflammatory (microglial) response to hydrogel-encapsulated grafts. In conclusion, IL-10-eluting collagen hydrogels may have beneficial anti-inflammatory effects in the context of cellular brain repair therapies for Parkinson’s disease and should be investigated further.

Publisher

Portland Press Ltd.

Subject

General Medicine

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