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Jianan Sun, Michiko Mandai, Hiroyuki Kamao, Masayo Takahashi; Protective effects of human iPS-derived retinal pigmented epithelial cells in comparison with human mesenchymal stromal cells and human neural stem cells on the degenerating retina in rd1 mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5749.
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© ARVO (1962-2015); The Authors (2016-present)
Retinitis pigmentosa, one of the leading causes of blindness, is a group of disorders that are characterized by progressive rod photoreceptor cell loss due to a genetic background. Major therapeutic strategies may include either preventing cell loss or replacing the lost photoreceptors. Pigment epithelium derived factor (PEDF) secreted predominantly by retinal pigmented epithelium (RPE) was reported to protect photoreceptors in retinal degeneration models. Also, clinical trials are under way outside Japan using human mesenchymal stromal cells (MSCs) and human neural stem cells (NSCs) to treat retinitis pigmentosa and dry age-related macular degeneration (AMD), respectively. Thus, the aim of this study was to investigate the rescue effects of RPE in comparison with those types of cells on photoreceptor degeneration in rd1 mice.
Three kinds of cells were each characterized using their markers and injected into the subretinal space (1×105cells/eye) of immune-suppressed 2 week old rd1 mice. We also tested neurotrophic factor secretion, such as PEDF, VEGF, TGF-beta and BDNF, by these cells using ELISA. We then counted the number of the remaining photoreceptor cells on post-operation day (POD) 14 and POD21. We evaluated the viability of grafts, the graft cell proliferation, apoptosis status and immune reaction against grafts as well. Moreover, we futher investigated the survival condition of grafted RPE cells 8 weeks and 12 weeks after transplantation.
Not only did iPS-derived RPE cells significantly avert the degeneration of photoreceptor cells on POD14 and POD21 compared with other two cell types (P< 0.05) but also were present in the subretinal space up to 12 weeks post-transplantation. RPE secreted significant amount of PEDF (240ng/ml/106cells/48h) and survived longer than the other cell type grafts with less immune responses and apoptosis.
iPS-derived RPE cells performed better rescue effects than MSC and NSC. This may be attributed to the secretion of PEDF and to the longer viability of iPS-derived RPE cells.
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