Title
Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates
UMMS Affiliation
Program in Molecular Medicine
Publication Date
2017-06-01
Document Type
Article
Disciplines
Biomaterials | Biomedical Devices and Instrumentation | Immunology and Infectious Disease | Medical Immunology
Abstract
Host recognition and immune-mediated foreign body response to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knockout and CXCL13 neutralization. Interestingly, colony stimulating factor-1 receptor (CSF1R) is significantly increased following implantation of multiple biomaterial classes: ceramic, polymer and hydrogel. Its inhibition, like macrophage depletion, leads to complete loss of fibrosis, but spares other macrophage functions such as wound healing, reactive oxygen species production and phagocytosis. Our results indicate that targeting CSF1R may allow for a more selective method of fibrosis inhibition, and improve biomaterial biocompatibility without the need for broad immunosuppression.
Keywords
Immunotherapy, Implants, Systems biology, Translational research
DOI of Published Version
10.1038/nmat4866
Source
Nat Mater. 2017 Jun;16(6):671-680. doi: 10.1038/nmat4866. Epub 2017 Mar 20. Link to article on publisher's site
Journal/Book/Conference Title
Nature materials
Related Resources
PubMed ID
28319612
Repository Citation
Doloff JC, Greiner DL, Anderson DG. (2017). Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates. Open Access Publications by UMass Chan Authors. https://doi.org/10.1038/nmat4866. Retrieved from https://escholarship.umassmed.edu/oapubs/3193
Comments
Full author list omitted for brevity. For the full list of authors, see article.