D. M. Irizarry1, C. D. Marshall1, D. Nguyen1, M. T. Longaker1,2, D. C. Wan1 1Stanford University Medical Center,Hagey Laboratory For Pediatric Regenerative Medicine,Palo Alto, CA, USA 2Stanford University Medical Center,Institute For Stem Cell Research And Regenerative Medicine,Palo Alto, CA, USA
Introduction:
Despite continued improvements in breast implant design, capsular contracture remains a significant problem. This is further worsened by adjuvant radiation therapy for breast cancer. Several studies have correlated fibroblast density with capsular contracture, and more recent reports have also shown a functional difference in fibroblasts from non-contracted and contracted breast implant capsules. Emerging data has now shown specific fibroblast subpopulations to exist, and in particular, CD26+ fibroblasts have been implicated in fibrosis/scarring following radiotherapy. The role of this fibroblast subpopulation in radiation-induced contracture was thus evaluated.
Methods:
Human breast capsule specimens were taken from patients following mastectomy with tissue expander placement and post-operative radiation therapy. The contralateral non-irradiated side served as a control. Capsules were mechanically and then enzymatically digested to obtain fibroblasts. Fluorescence-activated cell sorting and immunohistochemistry staining were performed. Cell surface marker expression and gene expression were compared between irradiated and non-irradiated specimens. Proportions of CD26+ fibroblasts were compared between the irradiated side and non-irradiated side.
Results:
Histology of the specimens revealed that irradiated, contracted capsule contained more dense eosinophilic material suggestive of smooth muscle tissue. Furthermore, irradiated, more severely contracted capsules were found to have more vimentin+/CD26+ cells by histology and flow cytometry. Gene analysis demonstrated differences in fibrotic gene expression between fibroblasts harvested from each side.
Conclusion:
These results suggest a role for CD26-expressing fibroblasts and smooth muscle cells in breast capsule contracture following radiation. These are both potential future targets for intervention aimed at reducing capsular contracture severity.