Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response
Name
sciadv.ade9488.pdf
Description
Published version
Size
1.38 MB
Format
Adobe PDF
Checksum (MD5)
ae35e2edcf0a0f660f516514b9ac1fe2
Author(s)
Doloff, Joshua C
Ma, Minglin
Sadraei, Atieh
Tam, Hok Hei
Farah, Shady
Hollister-Lock, Jennifer
Vegas, Arturo J
Veiseh, Omid
Quiroz, Victor M
Rakoski, Amanda
Date Issued
June 16, 2023
Journal
Science Advances
Publisher
American Association for the Advancement of Science
Citation
Joshua C. Doloff et al. ,Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response.Sci. Adv.9,eade9488(2023).
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/sciadv.ade9488
