Artificial reconstruction of fibre-shaped cellular constructs could greatly contribute to tissue assembly in vitro. Here we show that, by using a microfluidic device with double-coaxial laminar flow, metre-long core-shell hydrogel microfibres encapsulating ECM proteins and differentiated cells or somatic stem cells can be fabricated, and that the microfibres reconstitute intrinsic morphologies and functions of living tissues. We also show that these functional fibres can be assembled, by weaving and reeling, into macroscopic cellular structures with various spatial patterns. Moreover, fibres encapsulating primary pancreatic islet cells and transplanted through a microcatheter into the subrenal capsular space of diabetic mice normalized blood glucose concentrations for about two weeks. These microfibres may find use as templates for the reconstruction of fibre-shaped functional tissues that mimic muscle fibres, blood vessels or nerve networks in vivo.
Whilst being environmentally abundant, aluminum is not essential for life. On the contrary, aluminum is a widely recognized neurotoxin that inhibits more than 200 biologically important functions and causes various adverse effects in plants, animals, and humans. The relationship between aluminum exposure and neurodegenerative diseases, including dialysis encephalopathy, amyotrophic lateral sclerosis and Parkinsonism dementia in the Kii Peninsula and Guam, and Alzheimer's disease (AD) has been suggested. In particular, the link between aluminum and Alzheimer's disease has been the subject of scientific debate for several decades. However, the complex characteristics of aluminum bioavailability make it difficult to evaluate its toxicity and therefore, the relationship remains to be established. Mounting evidence has suggested that significance of oligomerization of β-amyloid protein and neurotoxicity in the molecular mechanism of AD pathogenesis. Aluminum may play crucial roles as a cross-linker in β-amyloid oligomerization. Here, we review the detailed characteristics of aluminum neurotoxicity based on our own studies and the recent literatures. Our aim is to revisit the link between aluminum and AD and to integrate aluminum and amyloid cascade hypotheses in the context of β-amyloid oligomerization and the interactions with other metals.
Microvilli are cellular membrane protrusions present on differentiated epithelial cells, which can sense and interact with the surrounding fluid environment. Biochemical and genetic approaches have identified a set of factors involved in microvilli formation; however, the underlying extrinsic regulatory mechanism of microvilli formation remains largely unknown. Here we demonstrate that fluid shear stress (FSS), an external mechanical cue, serves as a trigger for microvilli formation in human placental trophoblastic cells. We further reveal that the transient receptor potential, vanilloid family type-6 (TRPV6) calcium ion channel plays a critical role in flow-induced Ca2+ influx and microvilli formation. TRPV6 regulates phosphorylation of Ezrin via a Ca2+-dependent phosphorylation of Akt; this molecular event is necessary for microvillar localization of Ezrin in response to FSS. Our findings provide molecular insight into the microvilli-mediated mechanoresponsive cellular functions, such as epithelial absorption, signal perception and mechanotransduction.
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