The immunological profile of RC17 hESC-derived dopaminergic neural progenitor cells in vitro: implications for the STEM-PD clinical trial.
The immunological profile of RC17 hESC-derived dopaminergic neural progenitor cells in vitro: implications for the STEM-PD clinical trial.
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RC17 hESC 衍生的多巴胺能神经祖细胞的体外免疫学特征：对 STEM-PD 临床试验的影响。
DOI：
10.1101/2024.01.23.576826
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Curle A
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作者：
Curle A
帕金森病涉及多巴胺能神经元(DAN)的进行性丢失，促使临床试验用神经移植物取代细胞丢失。这包括多能干细胞来源的DAN祖细胞(NPC)的移植，目前正在STEM-PD试验中进行研究。为了确定移植后发生免疫排斥反应的可能性，我们对STEM-PD产品(RC17-hESC来源的NPC)的免疫原性进行了表征，并将它们与之前在试验中测试的人胎儿腹侧中脑组织(HfVM)进行了比较，其中包括我们自己的TRANSEURO试验。尽管促炎细胞因子上调了MHC-I类分子的表达，但在体外未检测到对NPC的免疫反应。相反，它们具有免疫抑制作用。转录分析显示，rc17-npc和hfvm之间有相似之处，都强烈上调了对干扰素γ反应的抗原处理和递呈途径。此外，免疫抑制剂霉酚酸酯在体外对鼻咽癌的存活和分化有不利影响。总体而言，我们的数据表明，hESC-NPC移植后不需要积极的免疫抑制，在选择免疫抑制方案时应谨慎行事。
Parkinson’s 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 detectedin 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 IFNγ. Furthermore, immunosuppressant mycophenolate mofetil detrimentally affected NPC survival and differentiationin 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.