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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

Studies to reveal correlation between terrain, energy use, and giraffe locomotion

2016-11-18

More than half of giraffes in captivity in Europe are afflicted by lameness. This high prevalence represents an important welfare issue, similar to other large zoo animals.

According to Dr Chris Basu, a veterinarian at the Royal Veterinary College in the UK, giraffes in captivity are often afflicted by overgrown hooves, laminitis and joint problems. Diagnosis and treatment is limited by our understanding of anatomy and function, more specifically the locomotion of these animals. Although the giraffe is such a well-known and iconic animal, relatively little has been studied about their locomotor behaviour.

Dr Basu recently visited South Africa to do fieldwork on the locomotion of giraffes as part of his PhD studies under the mentorship of world-renowned Professor of Evolutionary Biomechanics, Prof John Hutchinson. This project is a joint venture between Dr Basu and Dr Francois Deacon, researcher in the Department of Animal, Wildlife, and Grassland Sciences at the UFS. Dr Deacon is a specialist in giraffe habitat-related research.

Together Prof Hutchinson and Drs Deacon and Basu form a research group, working on studies about giraffe locomotion.

Wild giraffe population decrease by 40% in past decade

“Locomotion is one of the most common animal behaviours and comes with a significant daily energetic cost. Studying locomotion of wild animals aids us in making estimates of this energetic cost. Such estimates are useful in understanding how giraffes fit into ecosystems. Future conservation efforts will be influenced by knowledge of the energy demands in giraffes.

“Understanding aspects of giraffe locomotion also helps us to understand the relationships between anatomy, function and evolution. This is relevant to our basic understanding of the natural world, as well as to conservation and veterinary issues,” said Dr Deacon.

Locomotion study brings strategy for specialist foot care

On face value it seems as if foot disease pathologies are more common in zoo giraffes than in wild giraffes. “However, we need a good sample of data from both populations to prove this assumption,” said Dr Basu.

This phenomenon is not well understood at the moment, but it’s thought that diet, substrate (e.g. concrete, straw, sand and grass) and genetics play a part in foot disease in giraffes. “Understanding how the feet are mechanically loaded during common activities (standing, walking, running) gives our research group ideas of where the highest strains occur, and later how these can be reduced through corrective foot trimming,” said Dr Basu.

Through the studies on giraffe locomotion, the research group plans to devise strategies for corrective foot trimming. At the moment, foot trimming is done with the best evidence available, which is extrapolation from closely related animals such as cattle. “But we know that giraffes’ specialist anatomy will likely demand specialist foot care,” Dr Basu said.

Studying giraffes in smaller versus larger spaces

The research group has begun to study the biomechanics of giraffe walking by looking at the kinematics (the movement) and the kinetics (the forces involved in movement) during walking strides. For this he studied adult giraffes at three zoological parks in the UK.

However, due to the close proximity of fencing and buildings, it is not practical to study fast speeds in a zoo setting.

A setting such as the Willem Pretorius Nature Reserve, near Ventersburg in the Free State, Kwaggafontein Nature Reserve, near Colesberg in the Karoo, and the Woodland Hills Wildlife Estate in Bloemfontein are all ideal for studying crucial aspects such as “faster than walking” speeds and gaits to measure key parameters (such as stride length, step frequency and stride duration). These studies are important to understand how giraffe form and function are adapted to their full range of locomotor behaviours. It also helps to comprehend the limits on athletic capacity in giraffes and how these compare to other animals.

Drones open up unique opportunities for studying giraffes

The increasing availability of unmanned aerial vehicles (UAVs)/drones opens up unique opportunities for studying locomotion in animals like giraffes. Cameras mounted onto remotely controlled UAVs are a straightforward way to obtain high-quality video footage of giraffes while they run at different speeds.

“Using two UAVs, we have collected high definition slow motion video footage of galloping giraffes from three locations in the Free State. We have also collected detailed information about the terrain that the giraffes walked and ran across. From this we have created 3D maps of the ground. These maps will be used to examine the preferred terrain types for giraffes, and to see how different terrains affect their locomotion and energy use,” said Dr Deacon.

“The raw data (videos) will be digitised to obtain the stride parameters and limb angles of the animals. Later this will be combined with anatomical data and an estimation of limb forces to estimate the power output of the limbs and how that changes between different terrains,” said Dr Basu.

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