日本京都大学Jun Takahashi小组的一项最新研究揭示了基于iPSC的异基因细胞治疗帕金森病临床试验中免疫反应的控制。2025年8月19日，国际知名学术期刊《细胞—干细胞》发表了这一成果。

该研究团队最近进行了帕金森病主题异基因iPSCs细胞疗法的首个人体临床试验（jRCT编号：jRCT2090220384）。所有患者均通过他克莫司单独免疫抑制移植具有纯合子人白细胞抗原（HLA）单倍型的ipsc分化的多巴胺能神经祖细胞（iPSC-DANs）。无论HLA相容性如何，本研究均未观察到有临床意义的免疫反应。

然而，一个高度敏感的混合淋巴细胞反应主题，iPSC衍生的树突状细胞作为刺激物，证明了来自HLA错配受体的淋巴细胞的激活。这一发现表明，HLA在iPSC-DANs中的低表达有助于成功植入免疫特权中枢神经系统。这些结果表明，干细胞移植到中枢神经系统可能只需要适度的免疫抑制治疗。

研究人员表示，由于中枢神经系统（CNS）是一种免疫特权器官，与器官移植相比，诱导多能干细胞（iPSCs）的细胞治疗需要不同的免疫抑制策略。

附：英文原文

Title: Control of immune response in an iPSC-based allogeneic cell therapy clinical trial for Parkinson’s disease

Author: Asuka Morizane, Emi Yamasaki, Takero Shindo, Takayuki Anazawa, Nobukatsu Sawamoto, Atsushi Shima, Hodaka Yamakado, Etsuro Nakanishi, Masanori Sawamura, Yosuke Taruno, Daisuke Doi, Tetsuhiro Kikuchi, Yuri Kawasaki, Megumu K. Saito, Takayuki Kikuchi, Yoshiki Arakawa, Susumu Miyamoto, Yuji Nakamoto, Ryosuke Takahashi, Jun Takahashi

Issue&Volume: 2025-08-19

Abstract: Because the central nervous system (CNS) is an immune-privileged organ, it requires different immunosuppression strategies for cell therapies using induced pluripotent stem cells (iPSCs) compared with ones for organ transplantations. We recently conducted the first in-human clinical trial of a cell therapy for Parkinson’s disease using allogeneic iPSCs (jRCT number: jRCT2090220384). All patients were transplanted with dopaminergic neural progenitors differentiated from iPSCs (iPSC-DANs), which had homozygous human leukocyte antigen (HLA) haplotypes, through immunosuppression with tacrolimus alone. No clinically significant immune reaction was observed in this study, regardless of HLA compatibility. However, a highly sensitive mixed lymphocyte reaction using iPSC-derived dendritic cells as a stimulator demonstrated the activation of lymphocytes from HLA-mismatch-grafted recipients. This finding suggests that the low expression of HLA in iPSC-DANs contributes to successful engraftment in the immune-privileged CNS. These results indicate that only moderate immunosuppressive treatment may be required for stem cell transplantation to the CNS.

DOI: 10.1016/j.stem.2025.07.012

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00269-3