Building breast tissue in the lab to better understand lactation

Human breast milk is uniquely adapted to meet an infant¡¯s nutritional needs. Surprisingly, we still know very little about how milk is even made in the breast. A team of ETH Zurich researchers led by Marcy Zenobi-Wong, Professor of Tissue Engineering and Biofabrication, want to change that. In the lab, Zenobi-Wong and her team developed tiny replicas of lactating breast tissue. This involved isolating cells from human breast milk that are naturally found in milk. Some of the cells from lactating breast tissue and the so-called lactocytes ¨C the cells in breast tissue that produce milk ¨C end up in breast milk during lactation. 

Printed from real tissue using light

The centrepiece of the research project is a novel tissue model that the researchers produced using a special light printing process. The volumetric bioprinting process involves a laser beam that is shone into a liquid from several angles. The liquid then hardens precisely where the light dose accumulates. In seconds, this gives rise to small structures that are similar to real milk ducts and alveoli where the milk is produced in the breast. The material used comes from bovine udder tissue and contains similar components to human breast tissue. 

The researchers populated these mini milk ducts with cells that they extracted directly from human breast milk. These so-called mammary epithelial cells formed a dense layer of cells on the inside wall of the milk ducts. As the researchers were able to demonstrate, this resulted in functional tissue: the cells began producing typical milk components, such as ¦Â-casein and milk fat globules. ¡°It took several attempts to find out how we could best make the cells grow. Many of my colleagues were surprised to learn that milk-epithelial cells could grow at all,¡± says Amelia Hasenauer, doctoral student in Zenobi-Wong¡¯s team and first author of the external page study, published at the beginning of June in the journal Science Advances.

No artificial milk, but a key research instrument

Despite the impressive findings, the two researchers emphasise that they are not yet producing complete breast milk: ¡°We have identified the first components, but milk is made up of hundreds of different ones, including complex sugars, proteins, lipids, immune cells and living microorganisms,¡± says Zenobi-Wong. 

Hasenauer adds: ¡°Above all, our cell culture model is designed to help better understand the lactation process. I know many women who have struggled to breastfeed. Our model could one day help find answers.¡± The model is a key step forward for research. It allows lactating cells to be observed and manipulated under controlled conditions in the lab for the first time. This opens up an array of possibilities. Besides lactation research, other possible areas that could be studied are the impact of medications and chemicals on lactation and models of breast cancer. ¡°The next step is to increase the throughput of the milk collection, something which is achievable through 3D printing,¡± says Zenobi-Wong.

Greater visibility for aspects of female biology

The work by Zenobi-Wong¡¯s research group is an example of how little scientific research has been carried out on certain processes in the female body. Models like the new breast tissue printing could change that. Because unlike many other biomedical studies, this research isn¡¯t based on invasive surgery or animal experiments, but on cells that occur naturally in breast milk. This makes it easier, ethically justifiable and accessible to such research topics. 

Both researchers hope that their work will bring greater visibility not only to the topic of lactation, but also to a whole range of long-neglected areas of women¡¯s health. ¡°There are so many unanswered questions, from endometriosis to mastitis and fertility issues,¡± says Zenobi-Wong. ¡°It all warrants more scientific attention.¡±