Multipotent stem cells isolated from the adult mouse retina are capable of producing functional photoreceptor cells

• Published in: Cell research 2013-06, Vol.23 (6), p.788-802
• Main Authors: Li, Tianqing, Lewallen, Michelle, Chen, Shuyi, Yu, Wei, Zhang, Nian, Xie, Ting
• Format: Article
• Language: English
• Subjects: 631/154/51/1844/2319; 631/378/2613/1786; 631/532/2063; Animals; Biomedical and Life Sciences; Cell Biology; Cell Differentiation; Cell Proliferation; Cells, Cultured; Eye Proteins - metabolism; Homeodomain Proteins - metabolism; Life Sciences; Macular degeneration; Mice; Multipotent Stem Cells - metabolism; Multipotent Stem Cells - transplantation; Mutants; Nestin - metabolism; Original; original-article; Paired Box Transcription Factors - metabolism; PAX6 Transcription Factor; Photoreception; Photoreceptor Cells, Vertebrate - metabolism; Repressor Proteins - metabolism; Retina - cytology; Retina - metabolism; Retinal Degeneration - therapy; SOXB1 Transcription Factors - metabolism; Stem cells; Transplantation; Tumors; 光感受器; 分化潜能; 多能干细胞; 感光细胞; 成年小鼠; 突变小鼠; 细胞类型; 视网膜色素变性
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2013.48

Various stem cell types have been tested for their potential application in treating photoreceptor degenerative dis eases, such as retinitis pigmentosa （RP） and agerelated macular degeneration （AMD）. Only embryonic stem cells （ESCs） have so far been shown to generate functional photoreceptor cells restoring light response of photoreceptor deficient mice, but there is still some concern of tumor formation. In this study, we have successfully cultured Nestin＋Sox2＋Pax6＋ multipotent retinal stem cells （RSCs） from the adult mouse retina, which are capable of producing functional photoreceptor cells that restore the light response of photoreceptordeficient rdl mutant mice following transplantation. After they have been expanded for over 35 passages in the presence of FGF and EGF, the cultured RSCs still maintain stable proliferation and differentiation potential. Under proper differentiation conditions, they can differentiate into all the major retinal cell types found in the adult retina. More importantly, they can efficiently differentiate into photoreceptor cells under optimized differentiation conditions. Following transplantation into the subretinal space of slowly degenerating rd7 mutant eyes, RSCderived photoreceptor cells integrate into the retina, morphologically resembling endogenous photoreceptors and forming synapases with resident retinal neurons. When transplanted into eyes of photoreceptordeficient rdl mutant mice, a RP model, RSCderived photoreceptors can par tially restore light response, indicating that those RSCderived photoreceptors are functional. Finally, there is no evi dence for tumor formation in the photoreceptortransplanted eyes. Therefore, this study has demonstrated that RSCs isolated from the adult retina have the potential of producing functional photoreceptor cells that can potentially re store lost vision caused by loss of photoreceptor cells in RP and AMD.