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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

“My time at the UFS was the golden gem of my career”

2016-07-04

Description: Zig Gibson Tags: Zig Gibson

Prof Alan St Clair Gibson
Photo: Oteng Mpete

“My time at the University of the Free State (UFS) was the golden gem of my career. I have worked at medical schools or biomedical research centres in the United Kingdom, United States and at some of the top medical schools in South Africa, but working at the UFS was one of the highlights of my career,” says Prof Alan St Clair Gibson, Head of the UFS School of Medicine.

After spending just over two years at the UFS, Prof St Clair Gibson resigned from the institution in June 2016 and will take up the position of Dean: Health and Human Performance Sciences at the Waikato University in New Zealand in mid-July, where he will assist to establish a new faculty for all the health-science disciplines. “It was a privilege to work at the UFS. I come from a strong research background and wanted to grow research at the university, which I achieved. I came to the UFS because of the Academic and Human Projects and am proud of what has been achieved at the School of Medicine during the time I was here,” he said.

Prof St Clair Gibson highlighted some of these achievements, including the development of a management infrastructure across the disciplines of the school. “The establishment of an executive management committee for the school, as well as research champions in departments, highlighted the importance of proper governance and strategic management. By developing data dashboards, my management team and I could develop an understanding of research income and productivity, how the school works, what the role of teaching and learning is, and how the school could benefit in terms of third-stream income from the many contracts obtained by its academic staff. As a result, contracts and the financial management model of the school have also been reconfigured to the benefit of the university so that the institution and school can benefit from it,” he said.

His strong belief in an open-door policy has made staff feel part of the environment and it has created an atmosphere of equality and inclusivity. He believes in staff development and has, for instance, established leadership and management courses for heads of departments. Another factor to be proud of is the increase in the number of young researchers who recently joined the school, such as Prof Ross Tucker, who is one of the foremost sport scientists in the country. “It is a fact that staff retire or resign in all schools and departments of any university. It is also true that these departures offer opportunities to bring new academic and professional staff into the UFS. In fact, for the first time virtually every department in the School of Medicine now has a full-time Head of Department and 46 new staff were appointed since January 2015,” said Prof St Clair Gibson.

“I am especially proud of contributing, together with the senior leadership of the UFS, to stabilise the relationship with the Free State Department of Health (DoH). With the assistance of these parties, as well as my executive management team, we could find a better way of working together to the benefit of the school and the province.’’

Transforming the student profile to be representative of the country’s demographics is another milestone Prof St Clair Gibson will remember. “The intake of black and white students is of such a nature that we now have a much more balanced ratio of black and white undergraduate students than before.”

“I wanted to stay longer to see the effect of all the changes I made at the school, but the deanship is an offer I cannot refuse. I would have liked to see a steadier increase in the number of permanent clinical staff and have worked hard with both the UFS management and the DoH to try and achieve that; but more work needs to be done.”

I have worked with a number of fantastic staff members at the school, who are determined to do good in a challenging environment. I am amazed at the energy of the university leadership and how the Human and Academic Projects are executed. My wish for the university is to maintain and grow its standards and for the School of Medicine to maintain its reputation as one of the best schools in the country. I will always be a proud alumnus of the UFS,” he said.

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