Novel Hydrogel Scaffold Replicates Biologic Environment to Grow Human Breast Tissue

A new cell culture scaffold system supported human mammary tissue growth from patient-derived cells, according to a recent study published in Breast Cancer Research. The hydrogel scaffold system replicated human breast environment conditions and could be used to study breast development and the initiation and progression of breast cancer.1

The research team created a cell culture system that replicated important, physiologically relevant components of the breast without having to immortalize the cell lines. Nonimmortalization allowed the growth of cells from primary human cells. The hydrogel scaffold provides a 3-dimensional growth space for morphologically complex, hormone-responsive breast tissues from primary human breast epithelial cells.

Researchers obtained primary human breast epithelial cells from patient reduction mammoplasty tissues and seeded those cells into 3D hydrogels. Extracellular proteins and carbohydrates found in human breast tissue composed the hydrogel scaffold, creating a breastlike environment. Researchers monitored growth and assessed maturation based on morphology and immunostaining.

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Within 2 weeks of seeding cells in the hydrogel scaffolds, mature breast tissues formed. These tissues contained different breast cell types in the correct topological orientation. Additionally, mature breast tissues displayed complex ductal and lobular morphologies characteristic of the human breast.

Estrogen and progesterone administration caused the mature breast tissues to become hollow, and the addition of prolactin resulted in lipid droplet formation. Clusters of cells with putative breast stem cell markers initiated ductal branching. Leader cells preceded ductal elongation, protruding from duct tips to interact with the extracellular matrix.

"Ours is a beautiful system, and it's a very good tool for someone who has questions about normal breast development or breast cancer, to see what happens when a gene is perturbed. It's so amazing to watch the tissues grow," said Ethan Sokol, a graduate student at the Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, and lead author on the study.

This system could enable breast development and cancer research.

“We anticipate that this culture system will empower future studies of human mammary gland development and biology,” concluded the authors.

REFERENCE

1. Sokol ES, Miller DH, Breggia A, Spencer KC, Arendt LM, Gupta PB. Growth of human breast tissues from patient cells in 3D hydrogel scaffolds. Breast Cancer Res. 2016;18(1):19. doi:10.1186/s13058-016-0677-5.

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