Wang Zhenyu, Zhou Qingjun, Duan Haoyun, Wang Yao, Dong Muchen, Shi Weiyun
Qingdao University, Qingdao, Shandong, China.
Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, Shandong, China.
PLoS One. 2016 Mar 15;11(3):e0150731. doi: 10.1371/journal.pone.0150731. eCollection 2016.
Transplantation of ex vivo expanded corneal limbal stem cells (LSCs) has been the main treatment for limbal stem cell deficiency, although the shortage of donor corneal tissues remains a major concern for its wide application. Due to the development of tissue engineering, embryonic stem cells (ESCs)-derived corneal epithelial-like cells (ESC-CECs) become a new direction for this issue. However, the immunogenicity of ESC-CECs is a critical matter to be solved. In the present study, we explored the immunological properties of ESC-CECs, which were differentiated from ESCs. The results showed that ESC-CECs had a similar character and function with LSCs both in vitro and in vivo. In ESC-CECs, a large number of genes related with immune response were down-regulated. The expressions of MHC-I, MHC-II, and co-stimulatory molecules were low, but the expression of HLA-G was high. The ESC-CECs were less responsible for T cell proliferation and NK cell lysis in vitro, and there was less immune cell infiltration after transplantation in vivo compared with LSCs. Moreover, the immunological properties were not affected by interferon-γ. All these results indicated a low immunogenicity of ESC-CECs, and they can be promising in clinical use.
尽管供体角膜组织短缺仍然是其广泛应用的主要担忧，但体外扩增角膜缘干细胞（LSCs）移植一直是角膜缘干细胞缺乏症的主要治疗方法。由于组织工程的发展，胚胎干细胞（ESCs）来源的角膜上皮样细胞（ESC-CECs）成为解决这一问题的新方向。然而，ESC-CECs的免疫原性是一个亟待解决的关键问题。在本研究中，我们探讨了由ESCs分化而来的ESC-CECs的免疫学特性。结果表明，ESC-CECs在体外和体内均具有与LSCs相似的特征和功能。在ESC-CECs中，大量与免疫反应相关的基因被下调。MHC-I、MHC-II和共刺激分子的表达较低，但HLA-G的表达较高。ESC-CECs在体外对T细胞增殖和NK细胞裂解的反应较小，与LSCs相比，体内移植后免疫细胞浸润较少。此外，免疫学特性不受干扰素-γ的影响。所有这些结果表明ESC-CECs的免疫原性较低，它们在临床应用中可能很有前景。
