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Application of Cell‐Mate TM 3D matrix in modeling artificial breast ductal cancer as well as control “normal” tissues
Author(s) -
Lyden Timothy,
Justen Bruna Stilpen,
Loureiro Ronaldo
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1300.17
Subject(s) - spheroid , cell culture , hyaluronic acid , matrix (chemical analysis) , metastasis , cell , tissue engineering , extracellular matrix , breast cancer , chemistry , pathology , biology , cancer , biomedical engineering , medicine , microbiology and biotechnology , anatomy , biochemistry , genetics , chromatography
In collaboration with BRTI Life sciences, LLC., the UWRF TCIC has been engaged in testing and evaluating a new synthetic 3D tissue engineering matrix material product called Cell‐Mate. This new material is based on a combination of hyaluronic acid and chitosan which yields a final matrix gel that enmeshes cells at high densities to generate artificial tissue (AT) constructs. In this series of studies, breast ductal adenocarcinoma cells (MCF‐7) and “normal” breast ductal cells (MCF10A) were employed to generate significant artificial tissues based on the application of Cell‐Mate matrix materials. MCF‐7 ATs were generated from 40, 20 and 10 million cells respectively and MCF10A ATs were generated from 20 and 10 million cells. In all cases, successful ATs resulted with significant areas of tissue or tumor‐like architecture and distinct evidence of cellular differentiation as well as tumor development. MCF‐7 ATs generated evidence of tumor progression and eventual metastasis‐related spheroid, cluster and single cell release after 1–3 weeks of culture. In the case of 40 million cell seeding loads, spheroid production occurred within the first week of culture while at 20 and 10 million cell loads, the timing of spheroid generation/release was significantly longer at 2–3 weeks. However, within the first week, 20 million and 10 million cell loads did show definitive rounded features on the surfaces of the developing ATs. Interestingly, some cluster generation was also seen in the “normal” MCF10A cell line ATs as well, but at a much lower level. Also in the case of MCF10A, shed cells formed monolayers in the bottom of culture wells which displayed differentiation‐associated cells and colonies after 2–3 weeks of ATs development. These cells contrasted distinctly from those seen in the original culture monolayers which strongly supports the interpretation that ATs microenvironments induce pathway specific changes in cellular behaviors. Continuing studies are evaluating the morphology and marker expression profiles of tissues within the generated ATs as well as examining and comparing Cell‐Mate generated MCF‐7 spheroids in contrast to media induced or hanging drop culture generated spheroids. Based on studies to date, we propose the application of Cell‐Mate as an effective approach to modeling breast cancer tumors in‐vitro and expect that this will open the door to better understanding of the role of microenvironments in tumor development and progression generally.