Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response
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 b...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science
2024
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| Online Access: | https://hdl.handle.net/1721.1/156884 |
| _version_ | 1824458286917746688 |
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| author | 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 Aresta-DaSilva, Stephanie Bader, Andrew R Griffin, Marissa Weir, Gordon C Brehm, Michael A Shultz, Leonard D Langer, Robert Greiner, Dale L Anderson, Daniel G |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering 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 Aresta-DaSilva, Stephanie Bader, Andrew R Griffin, Marissa Weir, Gordon C Brehm, Michael A Shultz, Leonard D Langer, Robert Greiner, Dale L Anderson, Daniel G |
| author_sort | Doloff, Joshua C |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:03:32Z |
| format | Article |
| id | mit-1721.1/156884 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2025-02-19T04:23:29Z |
| publishDate | 2024 |
| publisher | American Association for the Advancement of Science |
| record_format | dspace |
| spelling | mit-1721.1/1568842025-01-03T04:47:54Z Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response 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 Aresta-DaSilva, Stephanie Bader, Andrew R Griffin, Marissa Weir, Gordon C Brehm, Michael A Shultz, Leonard D Langer, Robert Greiner, Dale L Anderson, Daniel G Massachusetts Institute of Technology. Department of Chemical Engineering 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. 2024-09-17T17:12:38Z 2024-09-17T17:12:38Z 2023-06-16 2024-09-17T16:58:16Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/156884 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). en 10.1126/sciadv.ade9488 Science Advances Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ application/pdf American Association for the Advancement of Science American Association for the Advancement of Science |
| spellingShingle | 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 Aresta-DaSilva, Stephanie Bader, Andrew R Griffin, Marissa Weir, Gordon C Brehm, Michael A Shultz, Leonard D Langer, Robert Greiner, Dale L Anderson, Daniel G Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response |
| title | Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response |
| title_full | Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response |
| title_fullStr | Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response |
| title_full_unstemmed | Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response |
| title_short | Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response |
| title_sort | identification of a humanized mouse model for functional testing of immune mediated biomaterial foreign body response |
| url | https://hdl.handle.net/1721.1/156884 |
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