How cell cultures are advancing medical research in NSW

The Non-Animal Technologies Network is driving innovation in health and medical research by advancing cutting-edge methods that better reflect how the human body responds to new treatments.

In 1906, the first successful animal cell culture was created using nerve cells from frogs. They were placed in test tubes containing blood, saline and agar – a gel-like substance made from red algae. Ross Granville Harrison, the biologist conducting this experiment at Johns Hopkins University, went on to become a pioneer in tissue culture.

Cut to the present, and the use of 2D cells grown in one layer in a Petri dish, is currently being replaced in some research by 3D cell cultures, which are grown in structures engineered to mimic human tissue. These and other advances in cell culture technology now underpin research such as drug discovery, safety and toxicity testing.

To further support these developments and be future-ready, the Non-Animal Technologies Network (NAT-Net) was established in 2024, with $4.5 million investment from the NSW Government and support from the Office for Health and Medical Research . NAT-Net, a collaboration co-founded by eight institutions across NSW, aims to promote the use of non-animal technologies to help reduce and replace the use of animals in research. It is administered by the University of New South Wales.

Reducing and replacing animals in research

“The research community is increasingly recognising limitations and ethical concerns associated with animal experimentation,” explains Associate Professor Adam Hill, co-founder and member of the Executive Committee that oversees the operation of NAT-Net.

Hill is a Laboratory head at the Victor Chang Cardiac Research Institute, one of the eight founding partners of NAT-Net. He is also Deputy Director of the Institute’s Innovation Centre, located in the St Vincent’s Health and Innovation Precinct.

“Non-animal models such as cell cultures, have the potential to enhance the predictive accuracy of human responses to new cutting-edge drug therapies. In doing so, in the longer term they may accelerate translation of research findings to clinical applications and so, help improve patient outcomes,” says Hill.

Learning from patient stem cells

The process of cell culture involves growing cells ‘in vitro’, (for example in a petri dish or in a flask), in a laboratory. Many different kinds of cells, including human stem cells, are used for cell cultures in health and medical research.

Stem cells are found in most tissues in the human body. They can replicate themselves and can also undergo a process called ‘differentiation’, where they change to become other types of cells. Patient cell samples (taken from blood, cells or skin) provide the human cells for Hill’s research after undergoing this differentiation process.

“These cells have to be collected and handled under approval from the relevant Human Research Ethics Committee,” says Hill. “They enable our research to utilise special heart muscle cells called cardiomyocytes, immune cells and fibroblasts, which are found in connective tissue. In turn, this allows us to work with a more realistic and functionally mature representation of the human heart, for disease modelling and drug screening.”

Progressing heart disease research

Atrial fibrillation is the primary focus of Hill’s current work. “This condition occurs when the upper chambers of the heart (called the atria), beat chaotically,” Hill explains.

Atrial fibrillation affects around 46 million people worldwide. The annual cost to the Australian healthcare system was recently estimated at $881 million, equivalent to 8.4% of recurrent expenditure on cardiovascular disease.

Hill’s research into this condition for the Victor Chang Cardiac Research Institute, has been supported by NAT-Net’s research pillar. “This support is helping to extend my work on modelling atrial fibrillation, to include more complex co-culture models and bioengineered tools,” says Hill. “After making engineered atrial tissues based on stem cells, we study how factors such as inflammation, obesity, and neuronal activity contribute to the mechanisms by which atrial fibrillation occurs.”

Harnessing new technologies for largescale cell culturing

Advanced equipment enables Hill and his team to grow many hundreds of millions of stem cell-derived heart cells to make 3D engineered tissues and organoids (mini organs made of 3D cells), for their heart research.

“For example, robotic liquid handling platforms allow us to automate processes of cell culture that used to be conducted in labs manually,” says Hill. “We also use ‘stirred tank bioreactors’ to grow much larger volume of cells in an environment controlled for optimal temperature, pH levels and nutrients, to help the cells grow.”