Novel Technique for Retinal Nerve Cell Regeneration with Electrophysiological Functions Using Human Iris-Derived iPS Cells

Cells

Natsuko Hatsusaka¹  Eri Kubo¹  Hiroshi Sasaki¹  Naoki Yamamoto¹  Shun Takeda¹  Masayuki Horiguchi²  Mahito Ohkuma³  Ei-ichi Miyachi³  Kazuyoshi Imaizumi⁴  Masashi Kondo⁴  Noriaki Nagai⁵  Noriko Hiramatsu⁶ 

[1] Department of Ophthalmology, Kanazawa Medical University, Ishikawa 920-0293, Japan;Department of Ophthalmology, School of Medicine, Fujita Health University, Aichi 470-1192, Japan;Department of Physiology, School of Medicine, Fujita Health University, Aichi 470-1192, Japan;Department of Respiratory Medicine, School of Medicine, Fujita Health University, Aichi 470-1192, Japan;Faculty of Pharmacy, Kindai University, Osaka 577-8502, Japan;Research Promotion and Support Headquarters, Fujita Health University, Aichi 470-1192, Japan;

关键词: human iris tissue stem/progenitor cells;    human iris-derived iPS cells;    p75NTR;    recoverin;    retinal ganglion cell;    electrophysiology;   

DOI  :  10.3390/cells10040743

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown