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Publication : Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response.

First Author  Doloff JC Year  2023
Journal  Sci Adv Volume  9
Issue  24 Pages  eade9488
PubMed ID  37327334 Mgi Jnum  J:352186
Mgi Id  MGI:7492911 Doi  10.1126/sciadv.ade9488
Citation  Doloff JC, et al. (2023) Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response. Sci Adv 9(24):eade9488
abstractText  Biomedical devices comprise a major component of modern medicine, however immune-mediated fibrosis and rejection can limit their function over time. Here, we describe a humanized mouse model that recapitulates fibrosis following biomaterial implantation. Cellular and cytokine responses to multiple biomaterials were evaluated across different implant sites. Human innate immune macrophages were verified as essential to biomaterial rejection in this model and were capable of cross-talk with mouse fibroblasts for collagen matrix deposition. Cytokine and cytokine receptor array analysis confirmed core signaling in the fibrotic cascade. Foreign body giant cell formation, often unobserved in mice, was also prominent. Last, high-resolution microscopy coupled with multiplexed antibody capture digital profiling analysis supplied spatial resolution of rejection responses. This model enables the study of human immune cell-mediated fibrosis and interactions with implanted biomaterials and devices.
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