Plastic Surgery Research Council

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CD26+ Fibroblast Subpopulations May Be Responsible For Radiation-Induced Breast Capsular Contracture
Dre M. Irizarry, MD, Clement Marshall, MD, Alessandra Moore, MD, Charles Blackshear, MD, Cristhan Montenegro, MS, Gordon K. Lee, MD, Dung Nguyen, MD, PharmD, Michael T. Longaker, MD, Derrick C. Wan, MD.
Stanford, Stanford, CA, USA.

PURPOSE: Breast implants, whether for augmentation or reconstruction, are associated with several well-known risks and complications, the most common of which is capsular contracture. Despite continued improvements in breast implant design, capsular contracture remains a significant problem with reported rates between 15% and 45%. The incidence as well as severity of contracture are 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. Our laboratory has been studying fibrosis in response to radiation treatment. In particular we published a paper in 2015 isolating fibroblast subpopulations which are responsible for scar formation, identified by engrailed 1 expression. We see with irradiated skin, that the bulk of the extracellular matrix is deposited by green engrailed 1 fibroblasts. We also identified CD26 as a cell surface marker that can enrich for engrailed 1 + fibroblasts. This was confirmed by concurrent staining for CD26 and green engrailed 1 fibroblasts. Based on these findings, we wanted to evaluate the role of CD26+ fibroblasts in irradiated breast capsules.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. Fluorescence-activated cell sorting and immunohistochemistry staining were performed Proportions of CD26+ fibroblasts were compared between the irradiated and non-irradiated specimens. RESULTS: We found thicker capsules on the irradiated side, as has already been described in the literature irradiated, more contracted capsules were found to have more vimentin+/CD26+ cells by histology and flow cytometry.
CONCLUSION: 96 800x600 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Arial",sans-serif;} These results suggest a role for CD26-expressing fibroblasts in breast capsule contracture following radiation. This are potential future targets for intervention aimed at reducing capsular contracture severity. This opens up the potential for use of CD26 inhibitors to possibly reduce the fibrotic response following radiation treatment.


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