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In vivo analysis of gene expression changes in mouse astrocytes after biomaterial injection into striatum

ABSTRACT: We conducted genome-wide RNA sequencing of immunoprecipitated specific ribosome-associated mRNA using RiboTag methods from mouse striatum following injection of a methyl cellulose biomaterial at 7, 14, 28, and 70 days after injection using AAV5 GfaABC1D-Rpl22HA to label astrocytes with RiboTag. Flow through samples were also processed to enable astrocyte gene enrichment analysis. Comparisons were also made between unloaded MC biomaterials and MC biomaterials delivering beta-hydroxybutyrate (BHB) at 7 and 28 days after injection. We also profiled transcriptomic responses of cultured mouse astrcoytes derived from differentiated mouse neural progenitor cells when fueled with BHB or glucose.

ORGANISM(S): Mus musculus

PROVIDER: GSE344979 | GEO | 2026/08/26

REPOSITORIES: GEO

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Project description:Biomaterials play an increasing role in clinical applications and regenerative medicine. Modern biomaterials should imitate the function of damaged tissue without triggering an immune response, initiate self-regeneration of the body and gradually degrade after implantation. The immune system is now well recognized to play a major role in influencing the biocompatibility of implanted medical devices. To develop a better understanding of the effects of biomaterials on the immune response, we have developed a highly sensitive novel test system capable of examining changes in the immune system by biomaterial. Here, we evaluate for the first time the immunopeptidome, a highly sensitive system that reflects cancer transformation, virus or drug influences and passes these changes directly to T cells, as a test system to examine the effects of contact with materials. Since monocytes are one of the first immune cells reacting to biomaterials, we have tested the influence of different materials - stainless steel, aluminum, zinc, high-density polyethylene, polyurethane films containing zinc diethyldithiocarbamate, copper, and zinc sulphate - on the monocytic THP-1 cell line. Material-associated peptides were identified after stimulation with all material types examined. The magnitude of induced changes in the immunopeptidome after the stimulation appears comparable to that of bacterial lipopolysaccharides (LPS). The source proteins of many detected peptides are associated with cytotoxicity, fibrosis, autoimmunity, inflammation and cellular stress. Considering all tested materials, it was found that the LPS-induced cytotoxicity-, inflammation- and cellular stress-associated HLA class I peptides were mainly induced by aluminum and HLA class II peptides mainly by stainless steel. These findings provide some of the first insights into the effects on the immunopeptidome by biomaterials. A more thorough understanding of these effects may enable the design of more biocompatible implant materials using in vitro models in future. This may be achieved through developing a deeper understanding of possible immune responses induced by biomaterials such as fibrosis, inflammation, cytotoxicity, and autoimmune reactions.

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In vivo analysis of gene expression changes in mouse astrocytes after biomaterial injection into striatum

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