Department of Ophthalmology, Kanazawa Medical University, Ishikawa 920-0293, Japan.
Graduate School of Health Sciences, Fujita Health University, Aichi 470-1192, Japan.
Cells. 2021 Mar 28;10(4):743. doi: 10.3390/cells10040743.
Regenerative medicine in ophthalmology that uses induced pluripotent stem cells (iPS) cells has been described, but those studies used iPS cells derived from fibroblasts. Here, we generated iPS cells derived from iris cells that develop from the same inner layer of the optic cup as the retina, to regenerate retinal nerves. We first identified cells positive for p75NTR, a marker of retinal tissue stem and progenitor cells, in human iris tissue. We then reprogrammed the cultured p75NTR-positive iris tissue stem/progenitor (H-iris stem/progenitor) cells to create iris-derived iPS (H-iris iPS) cells for the first time. These cells were positive for iPS cell markers and showed pluripotency to differentiate into three germ layers. When H-iris iPS cells were pre-differentiated into neural stem/progenitor cells, not all cells became positive for neural stem/progenitor and nerve cell markers. When these cells were pre-differentiated into neural stem/progenitor cells, sorted with p75NTR, and used as a medium for differentiating into retinal nerve cells, the cells differentiated into Recoverin-positive cells with electrophysiological functions. In a different medium, H-iris iPS cells differentiated into retinal ganglion cell marker-positive cells with electrophysiological functions. This is the first demonstration of H-iris iPS cells differentiating into retinal neurons that function physiologically as neurons.
眼科领域中使用诱导多能干细胞（iPS 细胞）的再生医学已经得到了描述，但这些研究使用的是源自成纤维细胞的 iPS 细胞。在这里，我们生成了源自虹膜细胞的 iPS 细胞，这些细胞与视网膜来自同一视神经杯的内层。我们首先在人眼虹膜组织中鉴定出了对 p75NTR 呈阳性的细胞，p75NTR 是视网膜组织干细胞和祖细胞的标志物。然后，我们首次将培养的 p75NTR 阳性虹膜组织干细胞/祖细胞（H-iris 干细胞/祖细胞）重编程为虹膜衍生的 iPS（H-iris iPS）细胞。这些细胞呈 iPS 细胞标志物阳性，并表现出向三个胚层分化的多能性。当 H-iris iPS 细胞预先分化为神经干细胞/祖细胞时，并非所有细胞都对神经干细胞/祖细胞和神经细胞标志物呈阳性。当这些细胞预先分化为神经干细胞/祖细胞，用 p75NTR 进行分选，并用作分化为视网膜神经细胞的培养基时，细胞分化为具有电生理功能的 Recoverin 阳性细胞。在另一种培养基中，H-iris iPS 细胞分化为具有电生理功能的视网膜节细胞标志物阳性细胞。这是首次证明 H-iris iPS 细胞分化为具有生理功能的视网膜神经元。
