MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates
MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates
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DOI：
10.1038/s41467-019-12324-0
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发表时间：
2019-09-25
影响因子：
16.6
通讯作者：
Perrier, Anselme L.
中科院分区：
文献类型：
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作者：
Badin, Romina Aron;Bugi, Aurore;Perrier, Anselme L.
来源于多能干细胞（iPSC）的细胞治疗产品（CTP）可能构成一种可再生的、特异性分化的细胞来源，有可能治愈患有神经退行性疾病的患者。然而，CTP的免疫原性仍然是基于移植非自体干细胞衍生的神经移植物的治疗方法的主要问题。尽管其相当大的副作用，长期的免疫抑制，似乎是必不可少的，以减轻神经炎症和防止排斥反应的同种异体CTP。已提出匹配iPSC供体和患者的HLA单倍型作为获得具有增强的免疫相容性的CTP的方式，最终减少对免疫抑制的需要。在目前的工作中，我们通过在亨廷顿病的灵长类动物模型中移植自体的、MHC匹配的和不匹配的神经元移植物来挑战这种范式。与以前的报告中unlesioned主机，我们表明，在没有免疫抑制MHC匹配单独是不足以授予长期生存的神经元移植在病变的大脑。
Cell therapy products (CTP) derived from pluripotent stem cells (iPSCs) may constitute a renewable, specifically differentiated source of cells to potentially cure patients with neurodegenerative disorders. However, the immunogenicity of CTP remains a major issue for therapeutic approaches based on transplantation of non-autologous stem cell-derived neural grafts. Despite its considerable side-effects, long-term immunosuppression, appears indispensable to mitigate neuro-inflammation and prevent rejection of allogeneic CTP. Matching iPSC donors' and patients' HLA haplotypes has been proposed as a way to access CTP with enhanced immunological compatibility, ultimately reducing the need for immunosuppression. In the present work, we challenge this paradigm by grafting autologous, MHC-matched and mis-matched neuronal grafts in a primate model of Huntington's disease. Unlike previous reports in unlesioned hosts, we show that in the absence of immunosuppression MHC matching alone is insufficient to grant long-term survival of neuronal grafts in the lesioned brain.