Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates.
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.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Joshua C
JC
Doloff
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Omid
0000-0003-1153-8079
O
Veiseh
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Arturo J
AJ
Vegas
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Hok Hei
HH
Tam
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Shady
S
Farah
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Minglin
M
Ma
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Jie
J
Li
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Andrew
A
Bader
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Alan
A
Chiu
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.
Atieh
A
Sadraei
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Stephanie
S
Aresta-Dasilva
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.
Marissa
M
Griffin
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Siddharth
S
Jhunjhunwala
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Matthew
M
Webber
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Sean
S
Siebert
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Katherine
K
Tang
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Michael
0000-0002-1590-768X
M
Chen
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Erin
E
Langan
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nimit
N
Dholokia
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Raj
R
Thakrar
Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
Meirigeng
M
Qi
Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
Jose
J
Oberholzer
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Dale L
DL
Greiner
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.|Division of Health Science Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.|Institute for Medical Engineering and Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Robert
R
Langer
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.|Division of Health Science Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.|Institute for Medical Engineering and Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Daniel G
DG
Anderson
D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects*; D005549:Foreign-Body Reaction / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D011323:Primates; D019736:Prostheses and Implants / Q000009:adverse effects*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*
D001672:Biocompatible Materials; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor