From two dimensions to three

“Traditionally in the health sciences we would grow 2D cell cultures, where the cells are grown on a flat surface like a culture dish,” says PhD student Claire Richards. Her supervisor, Dr Lana McClements, is leading the research project.  

“We might also use animal models or tissue obtained from the human placenta, though this can be difficult or incredibly risky to obtain, particularly early in pregnancy.

“In our 3D models, these cells can self-organise so that they can interact with others and their surrounding matrix in different directions. It helps them behave more like they would in the body.”

The research is based on cells known as trophoblasts, which are the main cell type in the placenta. Using the RASTRUM™ 3D bioprinter from Inventia Life Science, the researchers combine these trophoblast cells with a series of custom-made hydrogels, which are jelly-like substances that mimic the extracellular matrix.

The bioprinter prints tiny droplets into a tissue culture well plate and the resulting hydrogel structure supports the trophoblast cells to mature. Subsequently, with the help of associated cells, the trophoblasts organise themselves to form mini placenta structures known as trophoblast organoids.

These organoids provide a more robust model for the researchers to work with and offer new insights into the cellular and molecular processes of early pregnancy. The ultimate aim is to utilise these models to figure out how and why preeclampsia and other complications of pregnancy affected by placental dysfunction occur.

A true research-industry collaboration 

Currently, the researchers are working with Inventia to select the most appropriate hydrogel matrix ‘recipe’ from Inventia’s matrix library. The Inventia team have provided a series of formulations containing different protein combinations and at varying stiffnesses to be trialled in the work.

“With Claire’s project, at the moment we’re going through the process of selecting the right matrix, so she’s screening her cells against a variety of different additives to find the best combination for her cell types,” says Dr Alex Volkerling, a Customer Success Manager at Inventia Life Science who has been working closely with the UTS research team.

“Once we’ve successfully identified a matrix to support the trophoblast cells, we’ll assist in the experimental planning, if required, to help the research team produce the kind of data that will be valuable for their work.”

Delivering novel research answers

While the production of 3D models of the placenta using trophoblast cells is still in its infancy, the UTS team are hoping to demonstrate that their technique, in combination with Inventia’s 3D cell culture platform, can produce high-quality trophoblast organoids simply, reproducibly and at low cost.

“The cell line we’re working with is quite unique – only a few groups in the world have access to it through research collaboration,” says Dr McClements.

“Although bioprinting is now widespread, 3D bioprinted placental models are not very well known or developed; they’re still emerging, so this project is highly novel.”