Growth of Functional Breast Tissues

A hydrogel scaffold created by Whitehead Institute researchers so closely replicates the environment found within the human breast that the scaffold supports the growth of human mammary tissue from patient-derived cells

Whitehead Institute researchers have created a hydrogel scaffold replicating the environment found within the human breast. The scaffold supports the growth of human mammary tissue from patient-derived cells and can be used to study normal breast development as well as breast cancer initiation and progression.

Breast cancer research has been largely confined to studying transformed cell lines in a dish or implanting cells from established human tumors into mice and other animal models of the disease. Although these models provide some insight into a machinations of cancer at the cellular level, they fall short when investigating cancer initiation and progression within human tissue. For example, tumors recruit and rely on the cells and matrix surrounding them. In vitro cells are bereft of these environmental interactions, and although a mouse has mammary tissue, its structure differs vastly from that of a humans.

Whitehead Institute

Ideally, scientists would be able to grow in a dish human mammary glands that mimic the breast tissue of body, including its response to hormones that trigger development during pregnancy and lactation. Similar models are available for other human tissues, including intestine and brain, but establishing mammary models has proven problematic.

According to the prevailing belief at the time, mammary cells require other cells to support them and direct their development. Scientists thought that the molecules secreted by these cells might be more important than the support cells themselves. In pursuit of this hypothesis, they designed a hydrogel scaffold that so closely mimics the extracellular matrix of the breast that when it is seeded with
patient-derived primary human mammary cells, the cells organize themselves, grow, and differentiate into the ducts and lobes found in breast tissue. These mammary models also respond to steroid, pituitary, and lactogenic hormones that stimulate breast development.

The team, whose work is described this week in the journal Breast Cancer Research, has already gained intriguing insights into how mammary glands develop. According to their work, one or two leader mammary stem cells present at the tips of elongating ducts to direct ductal elongation. This method of expansion is quite different from that found in mouse mammary glands, which lack leader cells and grow through the activity of the luminal cells lining the ducts.

This work was supported by National Science Foundation Graduate Research Fellowships Program.

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