Advantages and challenges of using allogeneic vs. autologous sources for neuronal cell replacement in Parkinson’s disease: Insights from non-human primate studies

Intracerebral grafting of dopamine-producing cells is proposed as a strategy to replace the typical neurons lost to Parkinson’s disease (PD) and improve the typical PD motor symptoms. Non-human primate studies have provided clues on the relationship between host’s immune response and grafting success. Herein, we discuss how the host’s immune system differentially affects the graft depending on the origin of the cells and reflect on the advantages and limitations of the immune paradigms utilized to assess graft-related outcomes. We also consider new strategies to minimize or circumvent the host’s immunological response and related preclinical research needed to identify the most promising new approaches to be translated into the clinic. • Intracerebral grafts of dopamine-producing neurons derived from pluripotent stem cells are proposed for cell replacement in Parkinson’s disease. • The host’s immune system affects the success of the intracerebral grafting for both transplanted cell survival and integration. • Allogeneic and autologous cells present unique advantages and disadvantages for clinical application, including differences in their manufacturing, genomic stability, and capacity to elicit the host’s immune response. • New immunosuppression regimes, improved production of autologous cells, and genome modification of allogeneic cells for decreased immunogenicity are envisioned as solutions for clinical translation.