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4485 Silicone Implant Shells Increase the Rate of Proliferation of Patient-Derived BIA-ALCL Cells but Not Primary T Cells in an Engineered Biomimetic Breast Platform

OBJECTIVES/GOALS: We use a tissue engineered, biomimetic, 3D model to study the pathogenesis of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) by comparing the effect of silicone implant shell on proliferation of patient-derived BIA-ALCL to its precursor T cells within the breas...

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Autores principales: Premaratne, Ishani, Wright, Matthew, Gadjiko, Mariam, Lara, Daniel, Samadi, Arash, Ginter, Paula, Inghirami, Giorgio, Brown, Kristy, Spector, Jason
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823432/
http://dx.doi.org/10.1017/cts.2020.344
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author Premaratne, Ishani
Wright, Matthew
Gadjiko, Mariam
Lara, Daniel
Samadi, Arash
Ginter, Paula
Inghirami, Giorgio
Brown, Kristy
Spector, Jason
author_facet Premaratne, Ishani
Wright, Matthew
Gadjiko, Mariam
Lara, Daniel
Samadi, Arash
Ginter, Paula
Inghirami, Giorgio
Brown, Kristy
Spector, Jason
author_sort Premaratne, Ishani
collection PubMed
description OBJECTIVES/GOALS: We use a tissue engineered, biomimetic, 3D model to study the pathogenesis of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) by comparing the effect of silicone implant shell on proliferation of patient-derived BIA-ALCL to its precursor T cells within the breast microenvironment. METHODS/STUDY POPULATION: Patient-derived breast tissue was processed for 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 cells 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/ANTICIPATED RESULTS: Unstimulated T progenitor cell count showed no significant increase in any of the conditions tested. 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 revealed no significant increase in cell count over 8 days for all six conditions. Notably, our previous studies have shown proliferation of BIA-ALCL cells 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. DISCUSSION/SIGNIFICANCE OF IMPACT: Towards elucidating BIA-ALCL’s etiopathology, we show that silicone implant shell has a significant effect on proliferation of BIA-ALCL cells, but not their precursor T cells. If breast implant silicone shell is not a sufficient stimulus for T cell proliferation, co-stimulatory factors are required.
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spelling pubmed-88234322022-02-18 4485 Silicone Implant Shells Increase the Rate of Proliferation of Patient-Derived BIA-ALCL Cells but Not Primary T Cells in an Engineered Biomimetic Breast Platform Premaratne, Ishani Wright, Matthew Gadjiko, Mariam Lara, Daniel Samadi, Arash Ginter, Paula Inghirami, Giorgio Brown, Kristy Spector, Jason J Clin Transl Sci Precision Medicine OBJECTIVES/GOALS: We use a tissue engineered, biomimetic, 3D model to study the pathogenesis of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) by comparing the effect of silicone implant shell on proliferation of patient-derived BIA-ALCL to its precursor T cells within the breast microenvironment. METHODS/STUDY POPULATION: Patient-derived breast tissue was processed for 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 cells 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/ANTICIPATED RESULTS: Unstimulated T progenitor cell count showed no significant increase in any of the conditions tested. 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 revealed no significant increase in cell count over 8 days for all six conditions. Notably, our previous studies have shown proliferation of BIA-ALCL cells 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. DISCUSSION/SIGNIFICANCE OF IMPACT: Towards elucidating BIA-ALCL’s etiopathology, we show that silicone implant shell has a significant effect on proliferation of BIA-ALCL cells, but not their precursor T cells. If breast implant silicone shell is not a sufficient stimulus for T cell proliferation, co-stimulatory factors are required. Cambridge University Press 2020-07-29 /pmc/articles/PMC8823432/ http://dx.doi.org/10.1017/cts.2020.344 Text en © The Association for Clinical and Translational Science 2020 https://creativecommons.org/licenses/by/4.0/This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Precision Medicine
Premaratne, Ishani
Wright, Matthew
Gadjiko, Mariam
Lara, Daniel
Samadi, Arash
Ginter, Paula
Inghirami, Giorgio
Brown, Kristy
Spector, Jason
4485 Silicone Implant Shells Increase the Rate of Proliferation of Patient-Derived BIA-ALCL Cells but Not Primary T Cells in an Engineered Biomimetic Breast Platform
title 4485 Silicone Implant Shells Increase the Rate of Proliferation of Patient-Derived BIA-ALCL Cells but Not Primary T Cells in an Engineered Biomimetic Breast Platform
title_full 4485 Silicone Implant Shells Increase the Rate of Proliferation of Patient-Derived BIA-ALCL Cells but Not Primary T Cells in an Engineered Biomimetic Breast Platform
title_fullStr 4485 Silicone Implant Shells Increase the Rate of Proliferation of Patient-Derived BIA-ALCL Cells but Not Primary T Cells in an Engineered Biomimetic Breast Platform
title_full_unstemmed 4485 Silicone Implant Shells Increase the Rate of Proliferation of Patient-Derived BIA-ALCL Cells but Not Primary T Cells in an Engineered Biomimetic Breast Platform
title_short 4485 Silicone Implant Shells Increase the Rate of Proliferation of Patient-Derived BIA-ALCL Cells but Not Primary T Cells in an Engineered Biomimetic Breast Platform
title_sort 4485 silicone implant shells increase the rate of proliferation of patient-derived bia-alcl cells but not primary t cells in an engineered biomimetic breast platform
topic Precision Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823432/
http://dx.doi.org/10.1017/cts.2020.344
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