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Discerning Biomaterials-driven Transcriptome Dynamics to Induce Mesenchymal Stem Cell Differentiation

ABSTRACT: Bioactive materials harness the body’s innate regenerative potential by directing endogenous progenitor cells to facilitate tissue repair. Dissolution products of inorganic biomaterials provide unique biomolecular signaling for tissue-specific differentiation. We demonstrate the role of the inorganic biomaterial synthetic two-dimensional (2D) nanosilicates, and its ionic dissolution products on human mesenchymal stem cell differentiation. We utilize whole transcriptome sequencing (RNA-seq), to characterize the contribution of nanosilicates and its ionic dissolution products on endochondral differentiation. Our study highlights the modulatory role of ions in stem cell transcriptome dynamics by regulating lineage-specific gene expression patterns.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193172 | GEO | 2022/05/04

REPOSITORIES: GEO

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Project description:Nanowires (NWs), high-aspect-ratio nanomaterials, are increasingly used in technological materials and consumer products and may have toxicological characteristics distinct from nanoparticles. We carried out a comprehensive evaluation of the physicochemical stability of four silver nanowires (AgNWs) of two sizes and coatings and their toxicity to Daphnia magna. Inorganic aluminum-doped silica coatings were less effective than organic poly(vinyl pyrrolidone) coatings at preventing silver oxidation or Ag+ release and underwent a significant morphological transformation within 1 h following addition to low ionic strength Daphnia growth media. All AgNWs were highly toxic to D. magna but less toxic than ionic silver. Toxicity varied as a function of AgNW dimension, coating, and solution chemistry. Ag+ release in the media could not account for observed AgNW toxicity. Single-particle inductively coupled plasma mass spectrometry distinguished and quantified dissolved and nanoparticulate silver in microliter-scale volumes of Daphnia magna hemolymph with a limit of detection of approximately 10 ppb. The silver levels within the hemolymph of Daphnia exposed to both Ag+ and AgNW met or exceeded the initial concentration in the growth medium, indicating effective accumulation during filter feeding. Silver-rich particles were the predominant form of silver in hemolymph following exposure to both AgNWs and Ag+. Scanning electron microscopy imaging of dried hemolymph found both AgNWs and silver precipitates that were not present in the AgNW stock or the growth medium. Both organic and inorganic coatings on the AgNW were transformed during ingestion or absorption. Pathway, gene ontology, and clustering analyses of gene expression response indicated effects of AgNWs distinct from ionic silver on Daphnia magna. Four replicates each of five toxicant exposure groups of ~20 animals and four replicates of control, unexposed animals. Each control was compared to each exposed data set for a total of 16 comparisons per chemical condition.

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Discerning Biomaterials-driven Transcriptome Dynamics to Induce Mesenchymal Stem Cell Differentiation

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