Tissue mimetic 3D scaffold for breast tumor-derived organoid culture toward personalized chemotherapy

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 180; pp. 334 - 343
• Main Authors: Nayak, Biswadeep, Balachander, Gowri Manohari, Manjunath, Sathish, Rangarajan, Annapoorni, Chatterjee, Kaushik
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-08-2019
• Subjects: 3D culture; Biomimetic Materials - chemistry; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer associated fibroblasts; Cancer-Associated Fibroblasts - pathology; Cell Proliferation; Cell Survival - drug effects; Cell-Matrix Junctions - drug effects; Cell-Matrix Junctions - metabolism; Collagen Type I - pharmacology; Extracellular Matrix - metabolism; Female; Fibronectins - pharmacology; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Humans; Middle Aged; Organoids; Organoids - pathology; Personalized medicine; Polyesters; Porosity; Precision Medicine; Spheroids, Cellular - drug effects; Spheroids, Cellular - pathology; Tissue Culture Techniques; Tissue Scaffolds - chemistry; Tumor Cells, Cultured; Breast cancer; 3D culture; Cancer associated fibroblasts; Organoids; Personalized medicine
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2019.04.056

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•Porous scaffolds of polycaprolcatone (PCL) were prepared by particulate leaching.•Cancer associated fibroblasts (CAFs) were cultured in scaffolds to deposit proteins.•Protein coated PCL hybrid scaffolds were prepared by decellularization of CAFs.•Primary breast cancer cells proliferated on the scaffolds to form tumoroids.•Patient-specific response to cancer drugs were measured using the tumoroid cultures.
Breast cancer cell lines lose the inherent gene expression profiles of their source tumor and when cultured as monolayers (two-dimensional) are unable to represent patient tumors. Thus, we engineered a biochemico- and mechano-mimetic three-dimensional (3D) culture platform for primary breast cancer cells by decellularizing cancer-associated fibroblasts (CAFs) cultured on 3D macroporous polymer scaffolds to recapitulate tumor behavior and drug response more realistically. The presence of the CAF-derived extracellular matrix deposited on the polycaprolactone scaffold promoted cell attachment and viability, which is ascribed to higher levels of phosphorylated Focal Adhesion Kinase that mediates cell attachment via integrins. Single cells from primary breast cancers self-organized into tumoroids on prolonged culture. Response of the tumoroids to two chemotherapeutic drugs, doxorubicin and mitoxanthrone, varied significantly across patient samples. This model could be used as an ex vivo platform to culture primary cells toward developing effective and personalized chemotherapy regimens.