Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Department of Ophthalmology and Visual Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Int J Mol Sci. 2020 Oct 22;21(21):7831. doi: 10.3390/ijms21217831.
Retinal ganglion cells (RGCs) are impaired in patients such as those with glaucoma and optic neuritis, resulting in permanent vision loss. To restore visual function, development of RGC transplantation therapy is now underway. Induced pluripotent stem cells (iPSCs) are an important source of RGCs for human allogeneic transplantation. We therefore analyzed the immunological characteristics of iPSC-derived RGCs (iPSC-RGCs) to evaluate the possibility of rejection after RGC transplantation. We first assessed the expression of human leukocyte antigen (HLA) molecules on iPSC-RGCs using immunostaining, and then evaluated the effects of iPSC-RGCs to activate lymphocytes using the mixed lymphocyte reaction (MLR) and iPSC-RGC co-cultures. We observed low expression of HLA class I and no expression of HLA class II molecules on iPSC-RGCs. We also found that iPSC-RGCs strongly suppressed various inflammatory immune cells including activated T-cells in the MLR assay and that transforming growth factor-β2 produced by iPSC-RGCs played a critical role in suppression of inflammatory cells in vitro. Our data suggest that iPSC-RGCs have low immunogenicity, and immunosuppressive capacity on lymphocytes. Our study will contribute to predicting immune attacks after RGC transplantation.
视网膜神经节细胞(RGC)在青光眼和视神经炎等患者中受损,导致永久性视力丧失。为了恢复视觉功能,RGC 移植治疗的发展正在进行中。诱导多能干细胞(iPSC)是异体人源 RGC 移植的重要来源。因此,我们分析了 iPSC 衍生的 RGC(iPSC-RGC)的免疫学特性,以评估 RGC 移植后排斥的可能性。我们首先使用免疫染色评估 iPSC-RGC 上人白细胞抗原(HLA)分子的表达,然后使用混合淋巴细胞反应(MLR)和 iPSC-RGC 共培养评估 iPSC-RGC 激活淋巴细胞的效果。我们观察到 iPSC-RGC 上 HLA Ⅰ类分子表达较低,HLA Ⅱ类分子无表达。我们还发现,iPSC-RGC 在 MLR 测定中强烈抑制各种炎症免疫细胞,包括活化的 T 细胞,并且 iPSC-RGC 产生的转化生长因子-β2 在体外抑制炎症细胞中发挥关键作用。我们的数据表明 iPSC-RGC 具有低免疫原性和对淋巴细胞的免疫抑制能力。我们的研究将有助于预测 RGC 移植后的免疫攻击。