Silicone Implant Shells Increase The Rate Of Proliferation Of Patient-derived BIA-ALCL Cells But Not Primary T Cells In An Engineered Biomimetic Patient-derived Breast Tissue
Ishani D. Premaratne, BA, Matthew A. Wright, BA, Mariam Gadjiko, BA, Daniel O. Lara, BA, Arash Samadi, BA, Paula S. Ginter, MD, Giorgio Inghirami, MD, Kristy A. Brown, PhD, Jason A. Spector, MD.
Weill Cornell Medicine, New York, NY, USA.
PURPOSE: The pathogenesis of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) remains poorly understood. Our lab has demonstrated the power of studying BIA-ALCL behavior in a high-fidelity tissue engineered ex vivo biomimetic, three-dimensional model. Herein we use this model to compare the effect of silicone implant shell on proliferation of patient-derived BIA-ALCL cells to patient-derived T progenitor cells (from which ALCL originates) within the breast microenvironment.
METHODS: Patient-derived breast tissue was processed for its component adipocytes, ductal organoids, and stromal vascular fraction. These were suspended within 50 µl of 0.3% type I collagen matrix, to which was added 200,000 cells/mL of either patient-derived BIA-ALCL cells or T progenitor cells. These were then plated into 6mm wells. As a control, both BIA-ALCL and T progenitor cells were suspended within type I collagen alone at the same seeding density without breast components. Before plating, wells were lined circumferentially with either textured, smooth, or no implant shell. These were 1cm by 2cm pieces dissected from the whole implant. Wells were imaged using confocal microscopy over 8 days.
RESULTS: Unstimulated T progenitor cell count showed no significant increase in any of the conditions tested (Figure 1). The change in cell count over 8 days was 3.85% in each condition (p =0.3352). A Tukey’s multiple comparison test comparing each condition to each other additionally revealed no significant increase in cell count over 8 days for all conditions. The mean difference in cell count between days 0 and 4 was 214.1 cells (p = 0.559, 95% CI [-244.5, 672.6]), and between days 0 and 6 it was 229.1 cells (p =0.343, 95% CI [-148.8, 607.0]).
This can be compared to previous studies by our group where proliferation of BIA-ALCL cells was found to be significantly more robust in the biomimetic platform compared to collagen-only groups, regardless of implant shell type (p < 0.01). BIA-ALCL cells grew nearly 30% faster in textured and smooth shell biomimetic groups compared to biomimetic wells lacking implant shell (Figure 2).
CONCLUSION: Within a tissue-engineered 3D model of the breast microenvironment, unstimulated T progenitor cells showed no significant increase in proliferation regardless of the presence or absence of implant shell. Comparatively, BIA-ALCL cells proliferated more robustly in the presence of textured and smooth implant shell. Our data suggest that silicone implant shell has a significant and quantifiable effect on cell proliferation among pathologic BIA-ALCL cells, but not their precursor T cells. Thus, these data suggest that breast implant silicone shell alone is not a sufficient stimulus for T cell proliferation within the breast microenvironment, and imply that co-stimulatory factors are required. Further investigation into possible co-stimulatory factors are currently underway using our high-fidelity ex vivo model of the breast microenvironment.
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