Abstract

Volume.121 Number.11

Transplantation of Human Embryonic Stem Cell-derived Retinal Tissue in Primate Models of Photoreceptor Degeneration
Hiroshi Shirai
Department of Ophthalmology, Nagoya University Graduate School of Medicine

Retinitis pigmentosa is a genetic disease characterized by progressive degeneration of photoreceptors, which finally causes serious visual field loss. Effective treatments are limited for this disease. Photoreceptor transplantation therapy has been attracting growing interest after effectiveness of the therapy was demonstrated in rodent studies. Moreover, the recent development of protocols has allowed the culture of three-dimensional retinal tissue that is suitable for graft preparation with the use of human embryonic stem cells (hESCs) and human induced pluripotent stem cells. We have evaluated the clinical utility of hESC-derived retinal tissues (hESC-retina) in a stepwise manner. First, we confirmed the competency of hESC-retinas as a graft after transplantation into nude rats. We then developed two photoreceptor degeneration models in monkeys and evaluated the utility of the developed models. Finally, we transplanted hESC-retinas into the monkey models and confirmed structured graft maturation. Formation of host-graft synaptic connections was also suggested by immunohistological analysis. These results provide novel tools for the optimization of transplantation strategies for future clinical applications and demonstrate the clinical feasibility of hESC-retina transplantation.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 121: 837-846, 2017.

Key words
Human embryonic stem cell, Photoreceptor, Transplantation, Primate model
Reprint requests to
Hiroshi Shirai, M.D., Ph.D. Department of Ophthalmology, Nagoya University Graduate School of Medicine. 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan