TY - JOUR
T1 - Dissecting the recruitment and self-organization of αSMA-positive fibroblasts in the foreign body response
AU - Parlani, Maria
AU - Bedell, Matthew L.
AU - Mikos, Antonios G.
AU - Friedl, Peter
AU - Dondossola, Eleonora
N1 - Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved.
PY - 2022/12
Y1 - 2022/12
N2 - The foreign body response (FBR) is a clinically relevant issue that can cause malfunction of implanted medical devices by fibrotic encapsulation. Whereas inflammatory aspects of the FBR have been established, underlying fibroblast-dependent mechanisms remain unclear. We here combine multiphoton microscopy with ad hoc reporter mice expressing α–smooth muscle actin (αSMA) protein to determine the locoregional fibroblast dynamics, activation, and fibrotic encapsulation of polymeric materials. Fibroblasts invaded as individual cells and established a multicellular network, which transited to a two-compartment fibrotic response displaying an αSMA cold external capsule and a long-lasting, inner αSMA hot environment. The recruitment of fibroblasts and extent of fibrosis were only incompletely inhibited after depletion of macrophages, implicating coexistence of macrophage-dependent and macrophage-independent mediators. Furthermore, neither altering material type or porosity modulated αSMA+ cell recruitment and distribution. This identifies fibroblast activation and network formation toward a two-compartment FBR as a conserved, self-organizing process partially independent of macrophages.
AB - The foreign body response (FBR) is a clinically relevant issue that can cause malfunction of implanted medical devices by fibrotic encapsulation. Whereas inflammatory aspects of the FBR have been established, underlying fibroblast-dependent mechanisms remain unclear. We here combine multiphoton microscopy with ad hoc reporter mice expressing α–smooth muscle actin (αSMA) protein to determine the locoregional fibroblast dynamics, activation, and fibrotic encapsulation of polymeric materials. Fibroblasts invaded as individual cells and established a multicellular network, which transited to a two-compartment fibrotic response displaying an αSMA cold external capsule and a long-lasting, inner αSMA hot environment. The recruitment of fibroblasts and extent of fibrosis were only incompletely inhibited after depletion of macrophages, implicating coexistence of macrophage-dependent and macrophage-independent mediators. Furthermore, neither altering material type or porosity modulated αSMA+ cell recruitment and distribution. This identifies fibroblast activation and network formation toward a two-compartment FBR as a conserved, self-organizing process partially independent of macrophages.
UR - http://www.scopus.com/inward/record.url?scp=85144488559&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85144488559&partnerID=8YFLogxK
U2 - 10.1126/sciadv.add0014
DO - 10.1126/sciadv.add0014
M3 - Article
C2 - 36542704
AN - SCOPUS:85144488559
SN - 2375-2548
VL - 8
JO - Science Advances
JF - Science Advances
IS - 51
M1 - eadd0014
ER -