Cell-cell signaling in co-cultures of macrophages and fibroblasts

The foreign body response (FBR) comprises a general ubiquitous host tissue-based reaction to implanted materials In vitro cell-based models are frequently employed to study FBR mechanisms involving cell signaling responses to materials However these models often study only one cell type identify only limited signals and cannot accurately represent the complexity of in vivo inflammatory signaling To address this issue a cell co-culture system involving two primary effector cells of the FBR, macrophages and fibroblasts was employed Cell cell signaling systems were monitored between these cell types including long-term 1) culture of one cell type in conditioned media from the other cell type 2) non-contacting cell co-cultures (paracrine signaling) and 3) contact co-cultures (juxtacrine signaling) of primary- and secondary-derived cells Cell culture media and cell images were collected on Days 1 2 3 7 14 and 21 and changes in soluble protein secretion cellular behavior and morphology were assessed Primary- and secondary-derived cells responded uniquely during each signaling scenario and to one another In general higher in vitro fidelity to FBR-like responses was found in primary cell co-cultures compared to their mono-cultures and all secondary cell cultures (C) 2010 Elsevier Ltd All rights reserved