Enhanced Contraction of a Normal Breast-Derived Fibroblast–Populated Three-Dimensional Collagen Lattice via Contracted Capsule Fibroblast-Derived Paracrine Factors

Background: The authors’ aim was to identify morphological, genotypic, and cytokine profiles of normal breast-derived fibroblasts, noncontracted breast implant capsule (Baker grades 1 and 2) fibroblasts, and contracted breast implant capsule (Baker grades 3 and 4) fibroblasts, and to investigate the paracrine effects of contracted breast capsule fibroblast--conditioned media on a breast-derived fibroblast–populated three-dimensional collagen lattice. Methods: Primary breast-derived fibroblasts (n = 5), noncontracted breast capsule fibroblasts (n = 5), and contracted breast capsule fibroblasts (n = 5) were cultured, and conditioned media were obtained from passage 1 cells. Cells were immunostained for alpha smooth muscle actin to identify myofibroblasts. A panel of 16 inflammatory, fibrosis, extracellular matrix, and tissue remodeling–related genes were investigated using quantitative reverse transcriptase polymerase chain reaction and cytokine arrays. Fibroblast-populated collagen lattices were fabricated and treated with conditioned media, and lattice contracture was measured over 5 days. Results: Several inflammatory and fibrotic genes were significantly dysregulated in contracted breast capsule fibroblasts compared with noncontracted breast capsule fibroblasts and breast-derived fibroblasts (p < 0.05). Breast-derived fibroblast–populated collagen lattices treated with contracted breast capsule fibroblast–conditioned media demonstrated increased lattice contraction compared with treatment with normal 10% serum media (control), breast-derived fibroblasts, or noncontracted breast capsule fibroblast–conditioned media (p < 0.05). Breast-derived fibroblasts supplemented with contracted breast capsule fibroblast–conditioned media transformed into a contracted breast capsule fibroblast–like cell (p < 0.05). Conclusion: The authors show that contracted breast capsule–derived fibroblasts induce normal breast fibroblast transformation and contraction via paracrine signaling, which may contribute to capsular contracture formation.