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[IEEE 2018 IEEE Biomedical Circuits and Systems Conference (BioCAS) - Cleveland, OH, USA (2018.10.17-2018.10.19)] 2018 IEEE Biomedical Circuits and Systems Conference (BioCAS) - A μRadio CMOS Device for Real-Time In-Tissue Monitoring of Human Organoids
摘要： Human-derived brain organoids were proposed for the generation of functional in vitro models and human brain tissues for drug-discovery, precision medicine and cell-based clinical therapies. However, their generation is currently subjected to a high variability which limits their routine exploitation. To achieve a quality-controlled production of brain organoids and to provide readout capabilities for assays development, we propose to realize active micro-scale devices that can be embedded into living 3D cell assemblies to provide in-tissue wireless sensing and monitoring of biosignals. Here, we evaluate a low-power solution that integrates into a 100μm×100μm area all circuits required for sensing and amplification of bioelectrical signals while providing RF wireless power delivery and data transmission. Circuit simulations on a 130nm RF-CMOS node demonstrate the feasibility of such solution with a 6.18μW of power consumption. Preliminary in vitro experiments with dummy Si micro-devices demonstrate their integration into 3D cell aggregates during cell culture.
关键词： CMOS,low-power,RF,Human brain organoids,wireless biosensing
更新于2025-09-23 15:23:52
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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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Black Phosphorus Quantum Dots Cause Nephrotoxicity in Organoids, Mice, and Human Cells
摘要： Quantum dots (QDs) have numerous potential applications in lighting, engineering, and biomedicine. QDs are mainly excreted through the kidney due to their ultrasmall sizes; thus, the kidneys are target organs of QD toxicity. Here, an organoid screening platform is established and used to study the nephrotoxicity of QDs. Organoids are templated from monodisperse microfluidic Matrigel droplets and found to be homogeneous in both tissue structure and functional recapitulation within a population and suitable for the quantitative screening of toxic doses. Kidney organoids are proved displaying higher sensitivity than 2D-cultured cell lines. Similar to metal-containing QDs, black phosphorus (BP)-QDs are found to have moderate toxicity in the kidney organoids. The nephrotoxicity of BP-QDs are validated in both mice and human renal tubular epithelial cells. BP-QDs are also found to cause insulin insensitivity and endoplasmic reticulum (ER) stress in the kidney. Furthermore, ER stress-related IRE1α signaling is shown to mediate renal toxicity and insulin insensitivity caused by BP-QDs. In summary, this work demonstrates the use of constructed kidney organoids as 3D high-throughput screening tools to assess nanosafety and further illuminates the effects and molecular mechanisms of BP-QD nephrotoxicity. The findings will hopefully enable improvement of the safety of BP-QD applications.
关键词： kidney,organoids,nanosafety assessment,black phosphorus,quantum dots
更新于2025-09-23 15:19:57
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<i>De Novo</i> -Designed Near-Infrared Nanoaggregates for Super-Resolution Monitoring of Lysosomes in Cells, in Whole Organoids, and <i>in Vivo</i>
摘要： As the cleaners of cells, lysosomes play an important role in circulating organic matter within cells, recovering damaged organelles, and removing waste via endocytosis. Because lysosome dysfunction is associated with various diseases—lysosomal storage diseases, inherited diseases, rheumatoid arthritis, and even shock—it is vital to monitor the movement of lysosomes in cells and in vivo. To that purpose, a method of optical imaging, super-resolution imaging technology (e.g., SIM and STORM), can overcome the limitations of traditional optical imaging and afford a range of possibilities for fluorescence imaging. However, the short wavelength excitation and easy photobleaching of super-resolution fluorescence probes somewhat problematize super-resolution imaging. As described herein, we designed a low-toxicity, photostable, near-infrared small molecule fluorescence probe HD-Br for use in the super-resolution imaging of lysosomes. The interaction of lysosomes and mitochondria was dynamically traced while using the probe’s properties to label the lysosomes. Because the probe has the optimal near-infrared excitation and emission wavelengths, liver organoid 3D imaging and Caenorhabditis elegans imaging were also performed. Altogether, our findings indicate valuable approaches and techniques for super-resolution 3D and in vivo imaging.
关键词： lysosome-targeted,3D organoids imaging,C. elegans imaging,structured illumination microscopy,nanoaggregates
更新于2025-09-11 14:15:04
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Self-Formation of RPE Spheroids Facilitates Enrichment and Expansion of hiPSC-Derived RPE Generated on Retinal Organoid Induction Platform
摘要： PURPOSE. Retinal pigment epithelium (RPE) and neural retina could be generated concurrently through retinal organoid induction approaches using human induced pluripotent stem cells (hiPSCs), providing valuable sources for cell therapy of retinal degenerations. This study aims to enrich and expand hiPSC-RPE acquired with this platform and explore characteristics of serially passaged RPE cells. METHODS. RPE has been differentiated from hiPSCs with a published retinal organoid induction method. After detachment of neural retina on the 4th week, the remaining mixture was scraped from the dish and subjected to suspension culture for the formation of RPE spheroids. RPE sheets were isolated and digested for expansion. The cellular, molecular, and functional features of expanded RPE cells were evaluated by different assays. RESULTS. Under suspension culture, hiPSC-RPE spheroids with pigmentation self-formed were readily enriched by removing the non-retinal tissues. RPE sheets were further dissected and purified from the spheroids. The individualized RPE cells could be passaged every week for at least 5 times in serum medium, yielding large numbers of cells with high quality in a short period. In addition, when switched to a serum-free medium, the passaged RPE cells could mature in cellular, molecular, and physiological levels, including repigmentation, markers expression, and phagocytosis. CONCLUSIONS. We developed a simple and novel RPE spheroids formation approach to enrich and expand hiPSC-RPE cells generated along with retinal neurons on a universal retinal organoid induction platform. This achievement will reduce the cost and time in producing retinal cells for basic and translational researches, in particular for retinal cell therapy.
关键词： differentiation,human induced pluripotent stem cells,retinal pigment epithelium,retinal degenerations,organoids
更新于2025-09-11 14:15:04