Transplantation of neural progenitor cells (NPCs) is a potential therapy for treating neurodegenerative disorders, but this
approach has faced many challenges and limited success, primarily because of inhospitable host brain environments that
interfere with enriched neuron engraftment and function. Astrocytes play neurotrophic roles in the developing and adult
brain, making them potential candidates for helping with modification of hostile brain environments. In this study, we
examined whether astrocytic function could be utilized to overcome the current limitations of cell-based therapies in a murine
model of Parkinson’s disease (PD) that is characterized by dopamine (DA) neuron degeneration in the midbrain. We show
here that cografting astrocytes, especially those derived from the midbrain, remarkably enhanced NPC-based cell therapeutic
outcomes along with robust DA neuron engraftment in PD rats for at least 6 months after transplantation. We further show
that engineering of donor astrocytes with Nurr1 and Foxa2, transcription factors that were recently reported to polarize
harmful immunogenic glia into the neuroprotective form, further promoted the neurotrophic actions of grafted astrocytes in
the cell therapeutic approach. Collectively, these findings suggest that cografting astrocytes could be a potential strategy for
successful cell therapeutic outcomes in neurodegenerative disorders.