Effects of GDNF-Loaded Injectable Gelatin-Based Hydrogels on Endogenous Neural Progenitor Cell Migration

Brain repair following disease and injury is very limited due to difficulties in recruiting and mobilizing stem cells towards the lesion. More importantly, there is a lack of structural and trophic support to maintain viability of the limited stem/progenitor cells present. This study investigates the effectiveness of an injectable gelatin-based hydrogel in attracting neural progenitor cells (NPCs) from the subventricular zone (SVZ) towards the implant. Glial cell-line-derived neurotrophic factor (GDNF) encapsulated within the hydrogel and porosity within the hydrogel prevents glial scar formation. By directly targeting the hydrogel implant towards the SVZ, neuroblasts can actively migrate towards and along the implant tract. Significantly more doublecortin (DCX)-positive neuroblasts surround implants at 7 d post-implantation (dpi) compared with lesion alone controls, an effect that is enhanced when GDNF is incorporated into the hydrogels. Neuroblasts are not observed at the implant boundary at 21 dpi, indicating that neuroblast migration has halted, and neuroblasts have either matured or have not survived. The development of an injectable gelatin-based hydrogel has significant implications for the treatment of some neurodegenerative diseases and brain injuries. The ability of GDNF and porosity to effectively prevent glial scar formation will allow better integration and interaction between the implant and surrounding neural tissue.