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.
Retinitis pigmentosa (RP) is a group of visual impairments characterized by progressive rod photoreceptor cell loss due to a genetic background. Pigment epithelium-derived factor (PEDF) predominantly secreted by the retinal pigmented epithelium (RPE) has been reported to protect photoreceptors in retinal degeneration models, including rd1. In addition, clinical trials are currently underway outside Japan using human mesenchymal stromal cells and human neural stem cells to protect photoreceptors in RP and dry age-related macular degeneration, respectively. Thus, this study aimed to investigate the rescue effects of induced pluripotent stem (iPS)-RPE cells in comparison with those types of cells used in clinical trials on photoreceptor degeneration in rd1 mice. Cells were injected into the subretinal space of immune-suppressed 2-week-old rd1 mice. The results demonstrated that human iPS-RPE cells significantly attenuated photoreceptor degeneration on postoperative days (PODs) 14 and 21 and survived longer up to at least 12 weeks after operation than the other two types of graft cells with less immune responses and apoptosis. The mean PEDF concentration in the intraocular fluid in RPE-transplanted eyes was more than 1 µg/ml at PODs 14 and 21, and this may have contributed to the protective effect of RPE transplantation. Our findings suggest that iPS-RPE cells serve as a competent source to delay photoreceptor degeneration through stable survival in degenerating ocular environment and by releasing neuroprotective factors such as PEDF.
Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology (CDB), Kobe, Japan; Application Biology and Regenerative Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Jianan
J
Sun
Michiko
M
Mandai
Hiroyuki
H
Kamao
Tomoyo
T
Hashiguchi
Masayuki
M
Shikamura
Shin
S
Kawamata
Sunao
S
Sugita
Masayo
M
Takahashi
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D006085:Graft Survival; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D018696:Neuroprotective Agents / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D012162:Retinal Degeneration / Q000473:pathology / Q000628:therapy*; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D033581:Stem Cell Transplantation
D018696:Neuroprotective Agents
Cell-based therapy; Induced pluripotent stem cells; Pigment epithelium-derived factor; Retinal degeneration; Retinal pigment epithelium cells; Transplantation