| Autor: |
Mollinari C; Department of Neuroscience, Istituto Superiore di Sanita', 00161 Rome, Italy.; Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy., De Dominicis C; Department of Neuroscience, Istituto Superiore di Sanita', 00161 Rome, Italy.; Technoscience, 00166 Rome, Italy., Lupacchini L; IRCCS San Raffaele Roma, 00163 Rome, Italy., Sansone L; IRCCS San Raffaele Roma, 00163 Rome, Italy., Caprini D; Center for Life Nano and Neuro Sciences (CLN2S@Sapienza), Istituto Italiano di Tecnologia, 00161 Rome, Italy., Casciola CM; Department of Mechanical and Aerospace Engineering, Sapienza University of Rome, 00184 Roma, Italy., Wang Y; Lab of Regenerative Medicine and Neural Repair, Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Zhao J; Lab of Regenerative Medicine and Neural Repair, Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Fini M; IRCCS San Raffaele Roma, 00163 Rome, Italy., Russo M; IRCCS San Raffaele Roma, 00163 Rome, Italy.; MEBIC Consortium, San Raffaele University, 00166 Rome, Italy., Garaci E; IRCCS San Raffaele Roma, 00163 Rome, Italy.; San Raffaele Roma Open University, 00166 Rome, Italy., Merlo D; Department of Neuroscience, Istituto Superiore di Sanita', 00161 Rome, Italy. |
| Abstrakt: |
Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are clinically diagnosed using neuropsychological and cognitive tests, expensive neuroimaging-based approaches (MRI and PET) and invasive and time-consuming lumbar puncture for cerebrospinal fluid (CSF) sample collection to detect biomarkers. Thus, a rapid, simple and cost-effective approach to more easily access fluids and tissues is in great need. Here, we exploit the chemical direct reprogramming of patient skin fibroblasts into neurons (chemically induced neurons, ciNs) as a novel strategy for the rapid detection of different pathological markers of neurodegenerative diseases. We found that FAD fibroblasts have a reduced efficiency of reprogramming, and converted ciNs show a less complex neuronal network. In addition, ciNs from patients show misfolded protein accumulation and mitochondria ultrastructural abnormalities, biomarkers commonly associated with neurodegeneration. Moreover, for the first time, we show that microfluidic technology, in combination with chemical reprogramming, enables on-chip examination of disease pathological processes and may have important applications in diagnosis. In conclusion, ciNs on microfluidic devices represent a small-scale, non-invasive and cost-effective high-throughput tool for protein misfolding disease diagnosis and may be useful for new biomarker discovery, disease mechanism studies and design of personalised therapies. |
