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Aberrant hiPSCs-Derived from Human Keratinocytes Differentiates into 3D Retinal Organoids that Acquire Mature Photoreceptors
摘要： Human induced pluripotent stem cell (hiPSC)-derived three-dimensional retinal organoids are a new platform for studying the organoidogenesis. However, recurrent genomic aberration, acquired during generation of hiPSCs, limit its biomedical application and/or aberrant hiPSCs has not been evaluated for generation of differentiated derivatives, such as organoids and retinal pigment epithelium (RPE). In this study, we efficiently differentiated mosaic hiPSCs into retinal organoids containing mature photoreceptors. The feeder-free hiPSCs were generated from the human epidermal keratinocytes that were rapid in process with improved efficiency over several passages and maintained pluripotency. But, hiPSCs were cytogenetically mosaic with normal and abnormal karyotypes, while copy number variation analysis revealed the loss of chromosome 8q. Despite this abnormality, the stepwise differentiation of hiPSCs to form retinal organoids was autonomous and led to neuronal lamination. Furthermore, the use of a Notch inhibitor, DAPT, at an early timepoint from days 29–42 of culture improved the specification of the retinal neuron and the use of retinoic acid at days 70–120 led to the maturation of photoreceptors. hiPSC-derived retinal organoids acquired all subtypes of photoreceptors, such as RHODOPSIN, B-OPSIN and R/G-OPSIN. Additionally, the advanced maturation of photoreceptors was observed, revealing the development of specific sensory cilia and the formation of the outer-segment disc. This report is the first to show that hiPSCs with abnormal chromosomal content are permissive to the generation of three-dimensional retinal organoids.
关键词： genomic aberrations,keratinocytes,photoreceptors,retinal organoids,hiPSCs
更新于2025-09-23 15:22:29
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Sandwich-structure transferable free-form OLEDs for wearable and disposable skin wound photomedicine
摘要： Free-form optoelectronic devices can provide hyper-connectivity over space and time. However, most conformable optoelectronic devices can only be fabricated on flat polymeric materials using low-temperature processes, limiting their application and forms. This paper presents free-form optoelectronic devices that are not dependent on the shape or material. For medical applications, the transferable OLED (10 μm) is formed in a sandwich structure with an ultra-thin transferable barrier (4.8 μm). The results showed that the fabricated sandwich-structure transferable OLED (STOLED) exhibit the same high-efficiency performance on cylindrical-shaped materials and on materials such as textile and paper. Because the neutral axis is freely adjustable using the sandwich structure, the textile-based OLED achieved both folding reliability and washing reliability, as well as a long operating life (>150 h). When keratinocytes were irradiated with red STOLED light, cell proliferation and cell migration increased by 26 and 32%, respectively. In the skin equivalent model, the epidermis thickness was increased by 39%; additionally, in organ culture, not only was the skin area increased by 14%, but also, re-epithelialization was highly induced. Based on the results, the STOLED is expected to be applicable in various wearable and disposable photomedical devices.
关键词： Keratinocytes,Wearable photomedicine,Skin wound healing,Cell migration,Epidermis thickness,Re-epithelialization,Free-form optoelectronic devices,Sandwich-structure transferable OLED,Cell proliferation
更新于2025-09-12 10:27:22