Nav: Home

Engineered hydrogel scaffolds enable growth of functioning human breast tissue

March 01, 2016

CAMBRIDGE, Mass. (March 1, 2016) - 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.

"I wouldn't have thought it possible that these tissues could grow with such complexity and to such a size," says Whitehead Member Piyush Gupta, who is also an assistant professor of biology at MIT. "It's really quite remarkable."

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 cancer's machinations 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 human's.

Ideally, scientists would be able to grow in a dish human mammary glands that mimic the body's breast tissue, 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.

"It's been very hard to get primary human cells to stay alive, much less grow into tissues," says Daniel Miller, a graduate student in the Gupta lab.

When Gupta and his lab first attempted to culture human breast tissue, they thought that the problem might lie in the matrix or scaffold where the mammary glands were being grown. According to the prevailing belief at the time, mammary cells require other cells to support them and direct their development. Ethan Sokol and Miller thought that the molecules secreted by these cells might be more important than the support cells themselves. In pursuit of this hypothesis, Sokol and Miller 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.

"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," says Sokol. "It's so amazing to watch the tissues grow."
This work was supported by National Science Foundation Graduate Research Fellowships Program (NSFGRFP; 1122374).

Piyush Gupta's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also an assistant professor of biology at Massachusetts Institute of Technology.

Full Citation:

"Growth of human breast tissues from patient cells in 3D hydrogel scaffolds"

Breast Cancer Research, March 1, 2016.

Ethan S. Sokol (1,2,8), Daniel H. Miller (1,2,8), Anne Breggia (3), Kevin C. Spencer (4,5), Lisa M. Arendt (6), Piyush B. Gupta (1,2,4,7).

1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA

2. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

3. Maine Medical Center Research Institute, Scarborough, ME 04074, USA

4. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA

5. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

6. Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53711, USA

7. Harvard Stem Cell Institute, Cambridge, MA 02138, USA

8. Contributed to this work equally

Whitehead Institute for Biomedical Research

Related Breast Cancer Articles:

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.
Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.
Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.
More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.
Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.
Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.
Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.
Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.
Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.
Does MRI plus mammography improve detection of new breast cancer after breast conservation therapy?
A new article published by JAMA Oncology compares outcomes for combined mammography and MRI or ultrasonography screenings for new breast cancers in women who have previously undergone breast conservation surgery and radiotherapy for breast cancer initially diagnosed at 50 or younger.
More Breast Cancer News and Breast Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at     You can read The Transition Integrity Project's report here.