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Researchers developing 3D cell culture models to advance drug discovery

11 July 2024 | Story André Damons | Photo supplied

FARMVOS — From top (left to right): Dr Angélique Lewies (researcher from the Robert WM Frater Cardiovascular Research Centre within the UFS Department of Cardiothoracic Surgery), Zurika Murray (behavioural geneticist from the UFS Department of Genetics), Dr Marieka Gryzenhout (C-rated scientist and Senior Lecturer in the Department of Genetics), and Dr Jaco Wentzel (serves as the pharmaceutical industry partner and consultant for the project at FARMOVS).

In an effort to advance drug discovery and disease research, researchers from the University of the Free State (UFS), the Central University of Technology (CUT), and FARMOVS, a clinical research company associated with the UFS, is developing innovative 3D cell culture models using 3D printed mini bioreactors.

This interdisciplinary project, led by Dr Angélique Lewies, researcher from the Robert WM Frater Cardiovascular Research Centre (Frater Centre) within the UFS Department of Cardiothoracic Surgery, is creating more accurate and human-like models for this purpose, reducing the need for animal testing, and improving the safety and effectiveness of new treatments.

The project was initiated to address the challenges associated with current 3D cell culture techniques, which are often expensive and complex. Recognising the need for a more cost-effective and user-friendly solution, the researchers embarked on this collaboration to develop a novel 3D cell culture system. By making these advanced techniques more accessible, the team aims to enhance the reliability of drug testing and significantly reduce the reliance on animal experiments. This innovative approach not only promises to cut costs but also promotes ethical research practices in the scientific community.

Dr Lewies, whose research specialises in cardio-oncology (relationship between cancer treatment and heart health), particularly in understanding and preventing damage to cardiac cells caused by chemotherapy, leads the cell biology aspects of the project, focusing on the cultivation of 3D cancer spheroid and organoid cultures.

According to her, the project focuses on creating 3D cell cultures, known as spheroids and organoids, that mimic human tissues more closely. These 3D models can improve the reliability of drug testing and reduce the need for animal experiments, aligning with the 3R principles: Reduction, Replacement, and Refinement.

Creating a versatile platform

“Traditional drug discovery and disease studies often rely on flat (2D) cell cultures and animal models. While animal models are essential for understanding disease and testing drug safety, they don't always predict how humans will respond, and their use raises ethical concerns.

“We aim to develop affordable and efficient 3D-printed mini bioreactors for growing these advanced cell cultures. These bioreactors will be designed to fit into existing cell culture labs, making them accessible to researchers. By leveraging the cutting-edge 3D printing technology at CUT's Centre for Rapid Prototyping and Manufacturing (CRPM), the team hopes to create a versatile platform for various research applications,” says Dr Lewies.

She is joined in this project by UFS colleagues; Zurika Murray, a behavioural geneticist, and her colleague from the Department of Genetics, Dr Marieka Gryzenhout, a C-rated scientist and Senior Lecturer. Dr Jaco Wentzel from FARMOVS. is also involved in the project. Dr Wentzel serves as the pharmaceutical industry partner and consultant for the project. With experience in cellular biology and pharmaceuticals, he ensures that the new 3D cell culture models meet industry standards and can be effectively used in drug development. Dr Wentzel’s role is crucial in bridging the gap between academic research and practical application in the pharmaceutical industry.

Goals

According to Dr Lewies, this project aims to create more accurate and ethical models for drug testing and improving the development of new treatments. By combining expertise from engineering, biology, and mycology, the team is set to revolutionise how diseases are studied, and medicines developed. Funded by the CUT and UFS Joint Research Programme, this initiative promises to foster innovation and lead to new research collaborations.

“Cardiac cell damage, known as cardiotoxicity, can lead to serious cardiovascular diseases and is a major reason why some drugs are removed from the market. By developing 3D cancer spheroids and cardiac organoids (mini heart models), my team aims to find ways to prevent this cardiotoxicity while enhancing the effectiveness of chemotherapy drugs.

“Additionally, they are exploring the cardiotoxic effects of natural products, such as medicinal plants and mushrooms, which show potential for both anticancer and cardio-protective properties,” says Dr Lewies.

Experts

Murray is interested in how the psychedelic compounds psilocybin and psilocin affect the brain with her research focusing on the epigenome of genes within the serotonin pathway, which could explain the therapeutic potential of these compounds. “As part of this project, Murray will work with the Frater Centre to develop neuronal organoids (mini brain models) using the 3D mini-bioreactor platform.

“This will allow her to investigate the effects of psilocybin and psilocin on brain function, which have shown promise in treating mental health disorders like depression and anxiety, aiming to understand how these substances might help treat mental health issues,” says Dr Lewies.

Dr Gryzenhout brings her expertise in mycology and is responsible for cultivating medicinal mushrooms used in the project. Dr Gryzenhout's research focuses on the genetic characterisation of medicinal mushrooms and evaluating their therapeutic potential. These mushrooms produce a variety of bioactive compounds with therapeutic benefits, including anticancer activities, heart protection, and immune system support.

Her team is also approved by the South African Health Products Regulatory Authority (SAHPRA) to research the controlled psychedelic compounds psilocybin and psilocin.

Drug Discovery Goals

The project’s long-term focus is on potentially discovering new drugs to prevent and treat heart and brain diseases. Specifically, the team is working on developing therapies for cardio-oncology and neurological applications. In the realm of cardio-oncology, the goal is to find treatments that prevent cardiac cell damage and downstream cardiovascular diseases caused by cancer therapies, while still effectively targeting cancer cells. For neurological applications, the researchers are exploring the potential of drugs derived from medicinal mushrooms, including those with psychedelic properties, to treat conditions like depression, anxiety, and other mental health disorders.

News Archive

#Women'sMonth: Save the children

2017-08-10

Dr Trudi O’Neill, Senior lecturer in the Department of
Microbial, Biochemical and Food Biotechnology.
Photo: Anja Aucamp

Dr Trudi O’Neill, Senior lecturer in the Department of Microbial, Biochemical and Food Biotechnology, is conducting research on rotavirus vaccines.

Dr O’Neill was inspired to conduct research on this issue through her fascination with the virus. “The biology of rotaviruses, especially the genome structure and the virus’ interaction with the host, is fascinating.”

“In fact, it is estimated that, globally, ALL children will be infected with rotavirus before the age of five, irrespective of their socio-economic standing. However, infants and young children in poor countries are more vulnerable due to inadequate healthcare. The WHO estimates that approximately 215 000 deaths occur each year. This roughly equates to eight Airbus A380 planes, the largest commercial carrier with a capacity of approximately 500 seats, filled with only children under the age of five, crashing each week of every year.”

Alternative to expensive medicines
“Currently, there are two vaccines that have been licensed for global use. However, these vaccines are expensive and poor countries, where the need is the greatest, are struggling to introduce them sustainably. It is therefore appealing to study rotaviruses, as it is scientifically challenging, but could at the same time have an impact on child health,” Dr O’Neill said.

The main focus of Dr O’Neill’s research is to develop a more affordable vaccine that can promote child vaccination in countries/areas that cannot afford the current vaccines.

All about a different approach
When asked about the most profound finding of her research, Dr O’Neill responded: “It is not so much a finding, but rather the approach. My rotavirus research group is making use of yeast as vehicle to produce a sub-unit vaccine. These microbes are attractive, as they are relatively easy to manipulate and cheap to cultivate. Downstream production costs can therefore be reduced. The system we use was developed by my colleagues, Profs Koos Albertyn and Martie Smit, and allows for the potential use of any yeast. This enables us to screen a vast number of yeasts in order to identify the best yeast producer.”

Vaccination recently acquired a bad name in the media for its adverse side effects. As researcher, Dr O’Neill has this to say: “Vaccines save lives. By vaccinating your child, you don’t just protect your own child from a potentially deadly infection, but also other children in your community that might be too young to be vaccinated or have pre-existing health problems that prevents vaccination.”

A future without rotavirus vaccination?
Dr O’Neill believes a future without rotavirus vaccination will be a major step backwards, as the impact of rotavirus vaccines has been profound. “Studies in Mexico and Malawi actually show a reduction in deaths. A colleague in Mozambique has commented on the empty hospital beds that amazed both clinicians and scientists only one year after the introduction of the vaccine in that country. Although many parents, mostly in developed countries, don’t have to fear dehydrating diarrhoea and potential hospitalisation of their babies due to rotavirus infection anymore, such an infection could still be a death sentence in countries that have not been able to introduce the vaccine in their national vaccination programmes,” she said.

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