Potential of an injectable IL-10 rich collagen hydrogel for cell transplantation in Parkinson's Disease
Authors/Creators
- 1. Pharmacology and Therapeutics, National University of Ireland, Galway, Ireland
- 2. CÚRAM Centre for Research in Medical Devices, National University of Ireland, Galway, Ireland
Description
GDNF-enriched collagen hydrogels have shown to increase survival and re-innervation of grafted primary cells in rodent models Parkinson’s disease.1 Thus, the site specific delivery of neuroprotective and anti-inflammatory factors using an injectable biomaterial scaffold has the potential to target the main obstacles of the transplantation process such as poor cell survival and an elevated host immune response.
The aim of this study was to assess the biocompatibility of type 1 bovine collagen hydrogels of various cross-linker concentrations in vivo and the IL-10 release kinetics from these hydrogels.
In vitro, primary neural cultures were incubated with preformed collagen hydrogels for 24 h, and biocompatibility was assessed using cell viability assays and immunocytochemistry. In vivo, 24 male Sprague Dawley rats were given a bilateral intra-striatal delivery of 1000 ng of IL-10 as a bolus or encapsulated in collagen hydrogels. Polymerisation, biocompatibility, biodegradability and IL-10 retention were assessed at days 1, 2 and 4 using immunohistochemistry.
Collagen hydrogels were cytocompatible with primary neurons in vitro, successfully polymerised in situ in the brain, where they were also biocompatible and biodegradable. Most importantly, injection of IL-10 within the collagen hydrogel resulted in significant retention of the anti-inflammatory cytokine in the striatum, and reduced the host microglial response at the site of administration.
These studies highlight the potential of biomaterials for delivering anti-inflammatory cytokines to the brain which could benefit brain repair strategies for Parkinson’s disease.
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Additional details
Funding
References
- Moriarty N, Cabré S, Alamilla V, Pandit A, Dowd E. Encapsulation of young donor age dopaminergic grafts in a GDNF-loaded collagen hydrogel further increases their survival, re-innervation and functional efficacy after intra-striatal transplantation in hemi-Parkinsonian rats. European Journal of Neuroscience, 2018;001–10