Effects of GDF-5-loaded collagen hydrogels after intrastriatal transplantation of ventral mesencephalic cells in a rat model of Parkinson's disease.

Transplantation of dopaminergic neurons either harvested from foetal tissue or derived from various stem cell sources is a promising reparative therapy for Parkinson’s disease. However, such cell therapies are limited by poor survival and/or striatal reinnervation. Biomaterial hydrogels have the potential to improve these outcomes by acting as a physical scaffold for cell transplantation and as a reservoir system for neurotrophic factors. One potential neurotrophic factor to use in this context is growth differentiation factor 5 (GDF-5) which is a potent dopaminergic neuroprotective agent.

Therefore, this study sought to determine the survival and efficacy of primary dopaminergic grafts in a GDF-5-loaded collagen hydrogel in a rat model of Parkinson's disease.

Forty Sprague Dawley rats received a unilateral intra-MFB 6-OHDA lesion two weeks before transplantation surgery. They then received an intrastriatal transplant of E14 ventral mesencephalic (VM) cells (300 k per 6 µl) encapsulated in a collagen hydrogel which contained 20 µg per injection of GDF-5. Methamphetamine induced rotations were used to measure functional recovery at 4, 8 and 12 weeks after transplantation. Post-mortem assessment used immunohistochemistry for tyrosine hydroxylase, glial fibrillary acidic protein (GFAP), and OX-42 to identify graft survival, reinnervation, and host immune response.

We found that after transplantation, the GDF-5 functionalised collagen hydrogels did not significantly increase survival, reinnervation or functional recovery compared to transplantation of cells alone. The dose of GDF-5 used in this study was probably toxic to the transplanted cells.

In conclusion, the potential of functionalised collagen hydrogels and the effects of lower doses of GDF-5-loaded collagen hydrogels for the treatment of Parkinson’s disease should be further studied.