Mammary glands in a dish: Scientists recreate tissues for better models; spin out CRO planned

By Gareth Macdonald

- Last updated on GMT

Recreating tissues in vitro for better preclinical models
Recreating tissues in vitro for better preclinical models
Researchers say a hydrogel that prompts cells to form tissue-like structures in vitro could be used to make more accurate preclinical disease models.

The scientists – from Ludwig Maximilian University (LMU) and the Helmholtz Center in Munich, Germany – used the gel to construct mammary gland like structures from breast epithelial cells extracted from healthy donors.

Lead researcher Christina Scheel told us "we use a connective tissue component that is abundant in the human mammary gel to make a flexible hydrogel in which single cells generate multicellular structures with the same 3D architecture of the mammary gland.​"

The key for this to work is the composition of our growth medium and the fact that the cells can attach to the connective tissue fibres and contract the gel, something that also takes place during lactation to squeeze out the milk​.”

To date, the focus has been on using healthy cells to model normal tissues with the rationale being that “if your car breaks down and you want to repair it, you need to know how your car normally works​” Scheel said.

Modelling work

With this baseline now established, the team hopes to make disease models by manipulating the physical properties of gel and the genetics of the harvested cells.

Scheel explained that “we already know that if we make the gel very stiff, the cells do not make normal structures, but become invasive and spread, very similar to cancer.

What we are now setting up to do is to systematically perturb the biochemical and physical environment of the cells in the gel, and we will also genetically manipulate the cells and bring in mutations typical for breast cancer. Thereby, we can precisely model different aspects of normal mammary gland as well as breast cancer development​.”

The hydrogel technology can also be applied to other disease models Scheel said, explaining that: “There are many other tumours that derive from tissues that develop using similar principles as the mammary gland​” citing pancreatic adenocarcinoma as an example.

She added that: “Our assay can also be used to test compounds that promote regeneration for regenerative medicine approaches​.”

Tissue in a dish

In vitro tissue models are increasingly popular. San Diego, US–based Organovo’s use of 3D printing to produce human livers for preclinical toxicity testing​ has attracted the attention of Merck & Co​ and Johnson & Johnson’s (J&J) Janssen Research​ subsidiary.

The LMU and Helmholtz researchers plan to join this growing market by providing their tissue modelling services through a spin-off contract research organisation (CRO) for which they are currently seeking funding.

The cost of producing the bespoke assays is hard to estimate according to Scheel, who said: “Harvesting cells from one donor is about €500. One average donor will yield several hundreds of tests and generate several million breast-like structures.

Bringing the cells in culture and generating, in one test, about 100 structures will cost about €500 again. We are currently working on bringing the cost down by further miniaturising the assay.”

Source: Development 

“Quantification of regenerative potential in primary human mammary epithelial cells”

Linnemann, JR. et al.

DOI:10.1242/dev.123554

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