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

## TL;DR

This study shows that RC17 hESC-derived dopaminergic cells are not harmful to the immune system and may be safe for use in Parkinson's disease treatments.

## Contribution

The study introduces a framework for preclinical immune evaluation of stem cell therapies using in vitro assays.

## Key findings

- RC17 mesDA progenitors do not activate human T cells in vitro.
- mesDA progenitors suppress T cell activation and proliferation in co-culture.
- mesDA progenitors show equal or lower immunogenicity than human fetal VM tissue.

## Abstract

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.

•RC17 hESC-derived mesDA progenitors do not activate human T cells in vitro•mesDA progenitors suppress T cell activation and proliferation in co-culture•IFN-γ induces antigen presentation genes without inducing immunogenicity in vitro•mesDA progenitors show equal or lower immunogenicity than human fetal VM tissue

RC17 hESC-derived mesDA progenitors do not activate human T cells in vitro

mesDA progenitors suppress T cell activation and proliferation in co-culture

IFN-γ induces antigen presentation genes without inducing immunogenicity in vitro

mesDA progenitors show equal or lower immunogenicity than human fetal VM tissue

Human embryonic stem cell-derived dopaminergic progenitors (mesDA), prepared as in the STEM-PD trial for Parkinson’s, do not exhibit immunogenicity in vitro and instead actively suppress T cell activation in vitro. These findings support the immunological safety of RC17 mesDA progenitors and establish a functional framework for preclinical immune assessment of stem cell-based neural therapies.