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

Parkinson's disease involves the progressive loss of dopaminergic neurons, prompting clinical trials replacing cell loss with neural grafts. This includes the transplantation of pluripotent stem cell-derived mesencephalic dopaminergic neural progenitors (mesDAp), including the RC17 human embryonic stem cell (hESC)-derived cells currently under investigation in the European STEM-PD trial (NCT05635409). To assess potential immune rejection risk, we characterized RC17-mesDAp immunogenicity in vitro, comparing them to human fetal ventral mesencephalic tissue (hfVM), as successfully used in similar clinical trials such as TRANSEURO. Although RC17-mesDAp expressed MHC class I, upregulated by pro-inflammatory cytokines, no peripheral immune response was detected in vitro. Instead, cells exhibited immunomodulatory effects, reducing T cell CD25 expression and proliferation. Transcriptomic analysis showed that both RC17-mesDAp and hfVM upregulated antigen-processing pathways in response to IFN-γ yet remained non-immunogenic. Findings support the immunological safety of RC17-mesDAp and suggest a set of in vitro assays that may be applicable for the preclinical evaluation of other human stem cell therapies.