Directing the Self-assembly of Tumour Spheroids by Bioprinting Cellular Heterogeneous Models within Alginate/Gelatin Hydrogels

• Published in: Scientific reports Vol. 7; no. 1; pp. 4575 - 9
• Main Authors: Jiang, Tao, Munguia-Lopez, Jose G., Flores-Torres, Salvador, Grant, Joel, Vijayakumar, Sanahan, Leon-Rodriguez, Antonio De, Kinsella, Joseph M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-07-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/107; 631/61/2035; 631/67/70; 639/166/985; 639/301/54/2295; Alginates - chemistry; Alginic acid; Biomimetics; Bioprinting; Breast cancer; Cell culture; Cell migration; Coculture Techniques; Fibroblasts; Gelatin; Gelatin - chemistry; Humanities and Social Sciences; Humans; Hydrogels; Hydrogels - chemistry; multidisciplinary; Neoplasms - pathology; Science; Science (multidisciplinary); Self-assembly; Spheroids; Spheroids, Cellular - pathology; Spheroids, Cellular - ultrastructure; Tissue culture; Tissue Scaffolds - chemistry; Tumor Cells, Cultured - pathology; Tumor Cells, Cultured - ultrastructure; Tumor Microenvironment; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-04691-9

Human tumour progression is a dynamic process involving diverse biological and biochemical events such as genetic mutation and selection in addition to physical, chemical, and mechanical events occurring between cells and the tumour microenvironment. Using 3D bioprinting we have developed a method to embed MDA-MB-231 triple negative breast cancer cells, and IMR-90 fibroblast cells, within a cross-linked alginate/gelatin matrix at specific initial locations relative to each other. After 7 days of co-culture the MDA-MB-231 cells begin to form multicellular tumour spheroids (MCTS) that increase in size and frequency over time. After ~15 days the IMR-90 stromal fibroblast cells migrate through a non-cellularized region of the hydrogel matrix and infiltrate the MDA-MB-231 spheroids creating mixed MDA-MB-231/IMR-90 MCTS. This study provides a proof-of-concept that biomimetic
in vitro
tissue co-culture models bioprinted with both breast cancer cells and fibroblasts will result in MCTS that can be maintained for durations of several weeks.