Research press release



Stem cells: Replacing damaged nerves in Parkinson’s disease




これに関連して、移植後のiPS細胞由来ニューロンの生存期間を長くする方法を示した高橋たちのもう1つの論文がNature Communicationsに掲載される。高橋たちは、iPS細胞の主要組織適合遺伝子複合体(MHC)というタンパク質群をレシピエントのMHCと適合させることで、iPS細胞由来ニューロンに対する免疫応答を抑制して、移植されたニューロンの生存期間を長くできることを明らかにした。MHCは、免疫応答を誘導する役割を担っている。MHC適合だけで免疫応答を完全に防ぐことはできないため、高橋たちは、免疫抑制との併用を推奨しているが、MHC適合を実施することで免疫抑制剤の必要用量を減らし、投与期間を短縮できることも指摘している。

Restoration of nerve function in a monkey model of Parkinson’s disease, achieved using stem cell therapy, is demonstrated in this week’s Nature. The preclinical study shows that implantation of dopaminergic neurons derived from human induced pluripotent stem cells (iPSCs) can improve movement in affected monkeys. The results indicate that this approach could potentially be applied to the clinical treatment of human patients with Parkinson’s disease.

iPSCs are adult cells that have been reprogrammed to become capable of differentiating into a range of different cells. Human iPSCs are a promising source for cell-based therapy to replace damaged nerve cells in the brains of patients with neurological disease (in the case of Parkinson’s disease, nerve cells that use dopamine to communicate (dopaminergic neurons) are those that are damaged). To date, long-term study of human iPSC-derived dopaminergic neurons in primate models of Parkinson’s disease has not been performed. Thus, Jun Takahashi and colleagues assessed the safety and function of such neurons by implanting them into the brains of monkeys exhibiting a model of Parkinson’s disease. They show that these human-derived cells display long-term survival, function as midbrain dopaminergic neurons, and restore a range of movements. Regarding safety, the cells did not form any tumours in the brains for at least two years and elicited either no or only a mild immune response.

The number of surviving dopaminergic neurons varied between animals, and the authors identified genetic signatures that may affect survival, which could be used to select the best cell lines in a clinical setting. Further investigations will be needed to clarify the best markers for good donor cells, but the present results could contribute to the development of cell-based treatments for neurological diseases, the authors conclude.

In a related paper, published in Nature Communications, Takahashi and colleagues present an approach that improves the survival of iPSC-derived neurons after transplantation. They show that matching a group of proteins called the major histocompatibility complex (MHC) ― which have a role in eliciting immune responses ― in the iPSCs to the MHC of the recipient improves graft survival by reducing the immune response against the derived neurons. MHC matching does not completely prevent the immune response, so the authors propose that this approach should be used together with immunosuppression; however, they note that MHC matching could reduce the required dose and duration of immunosuppressive drugs.

doi: 10.1038/nature23664 | 英語の原文

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