Astrocytes, the most representative glial cells in the brain, play a multitude of crucial functions for proper neuronal development and synaptic‐network formation, including neuroprotection as well as physical and chemical support. However, little attention has been paid, in the neuroregenerative medicine and related fields, to the cytoprotective incorporation of astrocytes into neuron‐culture scaffolds and full‐fledged functional utilization of encapsulated astrocytes for controlled neuronal development. In this article, a 3D neurosupportive culture system for enhanced induction of neuronal circuit generation is reported, where astrocytes are confined in hydrogel microfibers and protected from the outside. The astrocyte‐encapsulated microfibers significantly accelerate the neurite outgrowth and guide its directionality, and enhance the synaptic formation, without any physical contact with the neurons. This astrocyte‐laden system provides a pivotal culture scaffold for advanced development of cell‐based therapeutics for neural injuries, such as spinal cord injury.
Collagen is a prominent target of nonenzymatic glycation, which is a hallmark of aging and causes functional alteration of the matrix. Here, we uncover glycation‐mediated structural and functional changes in the collagen‐enriched meningeal membrane of the human and mouse brain. Using an in vitro culture platform mimicking the meningeal membrane composed of fibrillar collagen, we showed that the accumulation of advanced glycation end products (AGEs) in the collagen membrane is responsible for glycation‐mediated matrix remodeling. These changes influence fibroblast‐matrix interactions, inducing cell‐mediated ECM remodeling. The adherence of meningeal fibroblasts to the glycated collagen membrane was mediated by the discoidin domain‐containing receptor 2 (DDR2), whereas integrin‐mediated adhesion was inhibited. A‐kinase anchoring protein 12 (AKAP12)‐positive meningeal fibroblasts in the meningeal membrane of aged mice exhibited substantially increased expression of DDR2 and depletion of integrin beta‐1 (ITGB1). In the glycated collagen membrane, meningeal fibroblasts increased the expression of matrix metalloproteinase 14 (MMP14) and less tissue inhibitor of metalloproteinase‐1 (TIMP1). In contrast, the cells exhibited decreased expression of type I collagen (COL1A1). These results suggest that glycation modification by meningeal fibroblasts is intimately linked to aging‐related structural and functional alterations in the meningeal membrane.
In article number 1901072 by Insung S. Choi and co‐workers, a 3D neuron‐culture system is fabricated by encapsulating astrocytes (green in the picture) in alginate microfibers and culturing hippocampal neurons (orange) on the aligned microfibers. The astrocyte‐laden microfibers enhance neurite outgrowth and synaptic formation as well as controlling the outgrowth directionality, suggesting a cytotherapeutic platform for neural injuries. The image was designed by co‐authors Sol Han and Hyunwoo Choi.
Spontaneous activation of macrophages in response to inflammation is a key part of innate immunity and host defense. Macrophages represent a heterogeneous population of cells with different phenotypic profiles performing distinct functions in host defense. Although a spectrum of macrophage activation stages exists in an inflamed region, the effect of local physical conditions on the heterotypic activation of macrophages is unknown. Here, we introduce an in vivo fluid–matrix interface analogous culture platform, an asymmetric microenvironment, facilitating the formation of macrophage aggregates (MAs). Macrophages were self-assembled to form MAs of ∼100 μm diameter at the collagen matrix–medium interface upon phorbol-12-myristate-13-acetate treatment. The macrophages within the half-embedded MAs into the matrix were heterogeneously activated, resulting in inhomogeneous cell–cell and cell–matrix interactions within the aggregates. Our demonstration may aid in a better understanding of the acquisition of macrophage heterogeneity in response to tissue-specific microenvironments.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.