Article

Protective Effects of Human iPS-Derived Retinal Pigment Epithelium Cell Transplantation in the Retinal Dystrophic Rat

Department of Ocular Biology and Therapeutics, Institute of Ophthalmology, University College London, London, United Kingdom.
PLoS ONE (Impact Factor: 3.23). 12/2009; 4(12):e8152. DOI: 10.1371/journal.pone.0008152
Source: PubMed

ABSTRACT

Transformation of somatic cells with a set of embryonic transcription factors produces cells with the pluripotent properties of embryonic stem cells (ESCs). These induced pluripotent stem (iPS) cells have the potential to differentiate into any cell type, making them a potential source from which to produce cells as a therapeutic platform for the treatment of a wide range of diseases. In many forms of human retinal disease, including age-related macular degeneration (AMD), the underlying pathogenesis resides within the support cells of the retina, the retinal pigment epithelium (RPE). As a monolayer of cells critical to photoreceptor function and survival, the RPE is an ideally accessible target for cellular therapy. Here we report the differentiation of human iPS cells into RPE. We found that differentiated iPS-RPE cells were morphologically similar to, and expressed numerous markers of developing and mature RPE cells. iPS-RPE are capable of phagocytosing photoreceptor material, in vitro and in vivo following transplantation into the Royal College of Surgeons (RCS) dystrophic rat. Our results demonstrate that iPS cells can be differentiated into functional iPS-RPE and that transplantation of these cells can facilitate the short-term maintenance of photoreceptors through phagocytosis of photoreceptor outer segments. Long-term visual function is maintained in this model of retinal disease even though the xenografted cells are eventually lost, suggesting a secondary protective host cellular response. These findings have identified an alternative source of replacement tissue for use in human retinal cellular therapies, and provide a new in vitro cellular model system in which to study RPE diseases affecting human patients.

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    • "Using iPSC technology to create the autologous source for cell therapy is an attractive strategy for regenerative medicine. Currently, most of the iPSC-based cell therapies are still tested in laboratory animal models, such as sickle cell anemia[103], spinal cord injury[104,105], age-related macular degeneration (AMD)[106], Parkinson's disease[107,108], and in non-human primates109110111112113. However, it has been demonstrated that human iPSCs could be used as a source of retinal pigment epithelial (RPE) cells for the treatment of AMD114115116. "
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    • "A recent followup study of the 18 patients involved in the trials revealed no serious safety issues related to the transplanted cells (Schwartz et al., 2015). Implantation of a single layer of stem-cell-derived RPE is another treatment approach currently under development (Carr et al., 2013; Idelson et al., 2009). Recently, a Japanese woman in her 70s was the first person to receive a transplanted layer of iPSC-RPE derived from her own skin cells (Cyranoski, 2014). "
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    • "ESC/iPSC can be induced to predominantly differentiate into RPE cells using similar protocols as above, but with the omission/antagonism of FGF to bias the generation of RPE cells over neural retina (Meyer et al., 2009, Osakada et al., 2009a). These ESC/iPSCderived RPE cells phagocytise photoreceptor outer segments(Carr et al., 2009a) and preserve retinal function in the RCS rats(Vugler et al., 2008, Carr et al., 2009b). A study comparing adult human ESC-derived RPE with foetal human RPE demonstrated a strong correlation in their gene expression profiles. "
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