Document Type
Article
Publication Date
6-16-2023
Original Citation
Doloff J,
Ma M,
Sadraei A,
Tam H,
Farah S,
Hollister-Lock J,
Vegas A,
Veiseh O,
Quiroz V,
Rakoski A,
Aresta-DaSilva S,
Bader A,
Griffin M,
Weir G,
Brehm M,
Shultz LD,
Langer R,
Greiner D,
Anderson D.
Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response. Sci Adv. 2023;9(24):eade9488.
Keywords
JMG, Humans, Animals, Mice, Biocompatible Materials, Foreign-Body Reaction, Disease Models, Animal, Foreign Bodies, Cytokines, Fibrosis
JAX Source
Sci Adv. 2023;9(24):eade9488.
ISSN
2375-2548
PMID
37327334
DOI
https://doi.org/10.1126/sciadv.ade9488
Grant
This work was supported by the Juvenile Diabetes Research Foundation (JDRF) (grants 17-2007-1063 and 1-PNF-2019-782-S-B) and National Institutes of Health (NIH) (grants EB000244, EB000351, DE013023, and CA151884). J.C.D. was supported by JDRF postdoctoral fellowship (grant 3-PDF-2015-91-A-N), and J.C.D. and V.M.Q. are supported by an FDA award FDA-21-RFQ-1245838. A.R. was supported by the NSF Graduate Research Fellowship Program (DGE-1746891). D.L.G., L.D.S., and M.A.B. are supported by the NIH UC4 DK104218, R24OD0426640, and R01AI132963 (M.A.B and L.D.S.).
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.
Comments
Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).