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bioRxiv · 10.1101/2024.01.23.576826

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

Curle, A. J.·Fazal, S. V.·Qarin, S.·Howlett, S. K.·He, X.·Barker, R. A.·Jones, J. L.
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Abstract

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 IFN{gamma}. 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.

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Curle, A. J., Fazal, S. V., Qarin, S., Howlett, S. K., He, X., Barker, R. A., Jones, J. L.. 2024-01-24. The immunological profile of RC17 hESC-derived dopaminergic neural progenitor cells in vitro: implications for the STEM-PD clinical trial.. https://doi.org/10.1101/2024.01.23.576826

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