MOE Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining 314400, China.
Int J Mol Sci. 2022 Aug 5;23(15):8722. doi: 10.3390/ijms23158722.
The loss of photoreceptors is a major event of retinal degeneration that accounts for most cases of untreatable blindness globally. To date, there are no efficient therapeutic approaches to treat this condition. In the present study, we aimed to investigate whether human amniotic epithelial stem cells (hAESCs) could serve as a novel seed cell source of photoreceptors for therapy. Here, a two-step treatment with combined Wnt, Nodal, and BMP inhibitors, followed by another cocktail of retinoic acid, taurine, and noggin induced photoreceptor-like cell differentiation of hAESCs. The differentiated cells demonstrated the morphology and signature marker expression of native photoreceptor cells and, intriguingly, bore very low levels of major histocompatibility complex (MHC) class II molecules and a high level of non-classical MHC class I molecule HLA-G. Importantly, subretinal transplantation of the hAESCs-derived PR-like cells leads to partial restoration of visual function and retinal structure in Royal College of Surgeon (RCS) rats, the classic preclinical model of retinal degeneration. Together, our results reveal hAESCs as a potential source of functional photoreceptor cells; the hAESCs-derived photoreceptor-like cells could be a promising cell-replacement candidate for therapy of retinal degeneration diseases.
感光细胞的丧失是视网膜变性的主要事件，占全球大多数不可治疗失明病例的原因。迄今为止，尚无有效的治疗方法来治疗这种疾病。在本研究中，我们旨在研究人羊膜上皮干细胞（hAESCs）是否可以用作治疗的新型感光细胞种子细胞来源。在这里，采用两步法处理，用 Wnt、Nodal 和 BMP 抑制剂联合处理，然后再用视黄酸、牛磺酸和 noggin 的混合物处理，诱导 hAESCs 向感光细胞样细胞分化。分化后的细胞表现出天然感光细胞的形态和特征标记物表达，有趣的是，它们具有非常低水平的主要组织相容性复合体（MHC）II 类分子和高水平的非经典 MHC I 类分子 HLA-G。重要的是，将 hAESCs 衍生的 PR 样细胞进行视网膜下移植可导致皇家外科医生学院（RCS）大鼠的部分视觉功能和视网膜结构恢复，这是视网膜变性的经典临床前模型。总之，我们的研究结果表明 hAESCs 是功能性感光细胞的潜在来源；hAESCs 衍生的感光细胞样细胞可能是治疗视网膜变性疾病的有前途的细胞替代候选物。
