期刊
STEM CELLS
卷 33, 期 8, 页码 2537-2549出版社
WILEY
DOI: 10.1002/stem.2032
关键词
Induced pluripotent stem cells; Retinal degeneration; Clinical translation; Progenitor cells; Stem cell transplantation
资金
- Simon and Beatrice Apple Stem Cell Fund for Eye Research
- David and Janet Polak Foundation Stem Cell Core Laboratory
- NIH [R01 EY020488]
- Department of Defense [W81XWH-12-1-0617]
- Foundation Fighting Blindness, Board of Governors Regenerative Medicine Institute at Cedars-Sinai Medical Center
- Knights Templar Eye Foundation, Inc.
- NATIONAL EYE INSTITUTE [R01EY020488] Funding Source: NIH RePORTER
Pluripotent stem cell-derived retinal pigment epithelial (RPE) cells are currently being tested for cell replacement in late-stage age-related macular degeneration (AMD). However, preserving vision at early-stages may also be possible. Here, we demonstrate that transplantation of neural progenitor cells (NPCs) derived from induced pluripotent stem cells (iNPCs) limits disease progression in the Royal College of Surgeons rat, a preclinical model of AMD. Grafted-iNPCs survived, remained undifferentiated, and distributed extensively in a laminar fashion in the subretinal space. Retinal pathology resulting from the accumulation of undigested photoreceptor outer segments (POS) was significantly reduced in iNPC-injected rats compared with controls. Phagosomes within grafted-iNPCs contained POS, suggesting that iNPCs had compensated for defective POS phagocytosis by host-RPE. The iNPC-treated eyes contained six to eight rows of photoreceptor nuclei that spanned up to 5mm in length in transverse retinal sections, compared with only one row of photoreceptors in controls. iNPC treatment fully preserved visual acuity measured by optokinetic response. Electrophysiological recordings revealed that retina with the best iNPC-protected areas were 140-fold more sensitive to light stimulation than equivalent areas of contralateral eyes. The results described here support the therapeutic utility of iNPCs as autologous grafts for early-stage of AMD.
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