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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

The launch of a unique conservation project

2011-06-06

Our Department of Animal, Wildlife and Grassland Sciences launched a very special pilot project at Woodland Hills Wildlife Estate in Bloemfontein on Friday 03 June 2011, which aims to eventually aid in the conservation and study of one of Africa’s most graceful animals.

The project aims to provide the scientific basis needed for making future decisions in the best interests of the giraffe in the Kgalagadi Transfrontier Park in the Northern Cape and involves collaring and monitoring the behaviour and movement of these animals via GPS.

Based on the public interest in the giraffe and the increased impact of the growing giraffe population on the vegetation in the area, SANParks has been considering the translocation of a number of Kgalagadi giraffe. Due to limited information regarding their adaptation success and potential impact on their new environment, thorough planning and subsequent monitoring of the species is required.

Mr Francois Deacon from our university decided to undertake a PhD study to address the existing challenges. This will be the first study of its kind, undertaken on giraffe.

He says he decided on this project because of his love for animals and conservation. “There are nine sub-species of giraffe and seven of these are already endangered. I want to involve people and make them aware of the plight of the animals and the need for conservation,” he said.

The project kicked off on Friday morning, with a group of students and curious nature-lovers tracking a herd of giraffe at Woodland Hills. The challenge laid in identifying one of the animals which could easily be collared with a GPS device, tranquilising it, and applying the device, without harming the animal.

After a young bull was identified, it was up to Dr Floris Coetzee, a veterinarian, to get close enough to the animal to tranquilise it, and to the group of students to catch it and hold it down. All this was done perfectly and the animal was fitted with its new collars. The collars were designed and made by Mr Martin Haupt, who gained extensive experience in the design of similar collars for other research studies.

Mr Deacon will spend the following two weeks personally monitoring the animal constantly, to ensure that the collars do not cause any discomfort or injury and to determine whether it should be removed or adapted.

It has taken Mr Deacon over a year to plan the collaring process and the associated study. He says the main challenges in the project are financial, since it will cost approximately R500 000 to run over five years.

Thus far he has been supported by Mr Pieter Malan of Woodland Hills, Mr Cas Kempff of Cas Kempff Consulting Engineers and Prof. Frans Swanepoel of the UFS’ Directorate of Research Development, all of whom have been benefactors of the project.
Information gathered from the pilot project will provide the data to assess how to best fit the collar onto the giraffe to ensure that the animal is comfortable and that the collar will last in the wild. Scientific data will be generated and processed for use by the Woodland Hills Wildlife Estate management.

Should the pilot project be successful, between four and eight giraffe in the Kgalagadi will be tracked using the satellite GPS collars. The GPS collars will enable the constant recording of the location of individual giraffe for up to 2 years. This will allow control and monitoring of the animals in real-time.

The main benefits of the project include, amongst others, improved decision-making, informing tourism development, education and community involvement, improved sustainability and improved cross-border collaboration between South Africa and Botswana.

Anyone who wishes to get involved with the project or get more information, should contact Me. Sonja Buhrmann at sbuhrmann@vodamail.co.za or 0827735768.

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