In vivo characterisation of an IL-10 rich collagen hydrogel scaffold for Parkinson's disease

Background: The main limitation of cell therapy in Parkinson’s disease is the poor graft survival upon transplantation. Biomaterials – like injectable collagen hydrogels – can help to enhance the survival of the grafted cells since they act as an adhesion matrix as well as a barrier from the host immune response.  The site specific delivery of anti-inflammatory factors using injectable biomaterial scaffolds has the potential to target the elevated inflammatory response present after cell transplantation therapy in Parkinson’s disease and therefore increase graft survival.

Aims: The aims of these studies were to assess if the collagen hydrogels could retain IL-10 in the striatum and if the IL-10 had any beneficial effects in cell survival, re-innervation and the host immune response.

Methods: In vivo, 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. In another in vivo study, parkinsonian rats were injected with primary dopaminergic cells (400.000 cells) with or without IL-10 (1000 ng) and in a collagen hydrogel or alone and were sacrificed 12 weeks post-transplantation. Graft survival, re-innervation and the host immune response were analysed.

Results: The 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 at early timepoints. Despite the fact that IL-10 reduced striatal microgliosis at 4 weeks post-transplantation, IL-10 did not increase cell survival in the grafts nor decrease the host immune response at 12 weeks after transplantation.

Conclusion: Although IL-10 is a potent anti-inflammatory cytokine that reduced the striatal microgliosis at early timepoints after transplantation, this fact did not have any effects in the long term survival of the grafted cells.

Acknowledgments: This project has been funded by the European Union Horizon 2020 Programme (H2020-MSCA-ITN-2015) under the Marie Sklodowska-Curie Innovative Training Networks and Grant Agreement No. 676408.