Enhanced Contraction of a Normal Breast-Derived Fibroblast-Populated Three-Dimensional Collagen Lattice via Contracted Capsule Fibroblast-Derived Paracrine Factors: Functional Significance in Capsular Contracture Formation

Plast Reconstr Surg. 2015 May;135(5):1413-1429. doi: 10.1097/PRS.0000000000001177.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / biosynthesis
  • Actins / genetics*
  • Breast / metabolism
  • Breast / pathology*
  • Breast Diseases / genetics
  • Breast Diseases / metabolism*
  • Breast Diseases / pathology
  • Cells, Cultured
  • Collagen*
  • Culture Media, Conditioned
  • Cytokines / biosynthesis
  • Cytokines / genetics*
  • DNA / genetics
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Fibrosis / genetics
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Flow Cytometry
  • Gene Expression Regulation*
  • Humans
  • Immunohistochemistry
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Actins
  • Culture Media, Conditioned
  • Cytokines
  • Collagen
  • DNA