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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

UFS Department of Physics offers unique learning experience with on-campus radio telescope

2015-12-14

Athanasius Ramaila, an Honours student in the Department of Physics, and Dr Brian van Soelen, a lecturer from the same department, in the laboratory where the radio telescope is housed in the new wing of the Physics Building on the Bloemfontein Campus of the UFS. The telescope will be used to expose graduate students to the basic techniques of radio astronomy.
Photo: Charl Devenish

The university this year added a four-storey wing to the existing Physics Building on the Bloemfontein Campus. The new development, which includes four lecture halls and four laboratories, complements other world-class facilities such as the X-ray photoelectron spectroscope and the scanning electron microscope.

A unique asset that distinguishes the UFS Department of Physics from other similar institutions, is the Boyden Observatory situated approximately 27 km northeast of Bloemfontein. The observatory houses a powerful 1.5 m optical telescope, and several smaller, but well equipped telescopes.

According to Pieter Meintjes, Professor in the Department of Physics, the observatory has acquired a new addition - a 0.5 m optical telescope donated by the South African Astronomical Observatory (SAAO) and the National Research Foundation (NRF) to the UFS Astrophysics Group. This optical telescope is one of two powerful optical telescopes used to introduce students to techniques such as photometry and spectroscopy.

“The telescope at Boyden forms an integral part of the Department of Physic’s student training and research programme. Because the UFS is the only university in South Africa operating such a facility, and one of only a few globally, Astrophysics students at the UFS have the unique privilege of having unrestricted access to these telescopes for their MSc and PhD studies,” says Prof Meintjes. In addition, the department has also built a radio telescope as part of a post-graduate student project. The telescope, housed in the new wing of the Physics Building at the Bloemfontein Campus of the UFS, will be used to expose graduate students to the basic techniques of radio astronomy, especially in light of the fact that the SKA is nascent. Prof Meintjes would like to act proactively by grounding his students in the relevant techniques of radio astronomy. The telescope will be used to introduce students to the manner in which radio flux calibrations are performed in order to determine the energy output of an emitting source.

At undergraduate level, the radio telescope will be used, together with optical telescopes in the Astrophysics laboratory, to place students at a high baseline regarding the level of multi-wavelength astrophysics training received at the UFS.

Third-year and Honours students will also have the opportunity of practical training in a research laboratory with 15 computers. The laboratory is equipped with software used to reduce and analyse multi-wavelength data.

“My goal is for the UFS to become the major centre of multi-wavelength astrophysics in South Africa and a key role player in the international arena. To be able to do this, our training should be world class,” Prof Meintjes said.

Aided by its world-class facilities and research, the Department of Physics is competing with the best in the world. Research-wise, a group from the Department of Physics is intensively involved with the SKA Project (Square Kilometre Array), with 3 000 dishes reaching from Carnavon in the Karoo to Mauritius in the Indian Ocean. According to Prof Meintjes, many detailed studies can be conducted with the SKA system of sources, showing major eruptions and mass effluent from the systems. Athanasius Ramaila, a BSc Honours student in Astrophysics at the UFS, has also received a two-year SKA internship, where he will be engaged in the SKA software engineering programme to help with developing software for the telescope.

The UFS Astrophysics Group is focusing on the multi-wavelength study of high-energy astrophysics sources. “This multi-wavelength approach to astrophysics is in line with the recent announcement by government that multi wavelength astrophysics will be the main focus for astrophysics research in South Africa. It is also a very important focus for research in the international arena, as can be seen from the large number of international conferences having a multi-wavelength character,” Prof Meintjes said.

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