Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates
Program in Molecular Medicine
Biomaterials | Biomedical Devices and Instrumentation | Immunology and Infectious Disease | Medical Immunology
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.
Immunotherapy, Implants, Systems biology, Translational research
DOI of Published Version
Nat Mater. 2017 Jun;16(6):671-680. doi: 10.1038/nmat4866. Epub 2017 Mar 20. Link to article on publisher's site
Doloff, Joshua C.; Greiner, Dale L.; and Anderson, Daniel G., "Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates" (2017). Open Access Articles. 3193.