The immunological profile of RC17 hESC-derived dopaminergic neural progenitor cells in vitro: implications for the STEM-PD clinical trial.

Parkinsons Disease involves the progressive loss of dopaminergic neurons (DAn), prompting clinical trials replacing cell loss with neural grafts. This includes the transplantation of pluripotent stem cell-derived DAn progenitor cells (NPC) currently under investigation in the STEM-PD trial. To determine the likelihood of immune rejection post-grafting, we characterised the immunogenicity of the STEM-PD product (RC17-hESC-derived NPCs), comparing them to human foetal ventral mesencephalic tissue (hfVM) previously tested in trials, including our own TRANSEURO trial. Despite MHC-Class I expression, upregulated by proinflammatory cytokines, no immune response to NPCs was detected in vitro. Instead, they were immunosuppressive. Transcriptomic analysis revealed similarities between RC17-NPCs and hfVM, both strongly upregulating antigen processing and presentation pathways in response to IFNgamma. Furthermore, immunosuppressant mycophenolate mofetil detrimentally affected NPC survival and differentiation in vitro. Overall, our data suggest that aggressive immunosuppression is not required following hESC-NPC transplantation and that caution should be exercised when selecting the immunosuppressive regimen. ### Competing Interest Statement R.A.B has provided consultancy advice around dopamine cell-based therapies to Aspen Neuroscience, BlueRock Therapeutics, FCDI and Novo Nordisk. J.L.J reports consultancy work for Enhanc3DGenomics, Sanofi and Roche. S.Q. is a current employee at Insmed Inc.