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.
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).


CONCLUSIONS
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.
Manchester, United Kingdom From Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester; and the Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Center.
Daniel J T
DJT
Kyle
Ardeshir
A
Bayat
D000199:Actins / Q000096:biosynthesis / Q000235:genetics*; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001941:Breast Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003094:Collagen; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; D017077:Culture Media, Conditioned; D016207:Cytokines; D003094:Collagen; D004247:DNA