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11 July 2024 | Story André Damons | Photo supplied
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

Moshoeshoe - lessons from an African icon - by Prof Frederick Fourie
2004-11-03

(The full text of the article that appeared in City Press and Sunday Independent)

Our understanding of history informs our understanding of the present. No wonder the contestation over historical figures in South Africa’s past is so fierce and so divisive.
The question is: could it be any other way? I would like to think that it could; that black and white South Africans, across linguistic, cultural, religious and other divides, can develop a shared appreciation of our history – at least with certain periods and personalities as a starting point.

One such personality whose legacy I believe offers a possible platform for unifying our still divided country is King Moshoeshoe, who lived from 1786 to 1870, and is acknowledged as the founder of the Basotho.

King Moshoeshoe is the topic of a documentary that has been commissioned by the University of the Free State as part of its Centenary celebrations this year. It is part of a larger project to honour and research the legacy of Moshoeshoe. The documentary will be screened on SABC 2 at 21:00 on November 4th.

Moshoeshoe rose to prominence at a time of great upheaval and conflict in South Africa – the 19th century, a time when British colonialism was entrenching itself, when the Boer trekkers were migrating from the Cape and when numerous indigenous chiefdoms and groupings were engaged in territorial conquests. It was the time of the Difaqane, a period when society in the central parts of the later South Africa and Lesotho was fractured, destabilised and caught in a cycle of violence and aggression.

In this period Moshoeshoe displayed a unique and innovative model of leadership that resulted in reconciliation, peace and stability in the area that later became Lesotho and Free State. It made him stand out from many of his contemporaries and also caught the attention of his colonial adversaries.

Such an evaluation is not a judgment about which model of leadership is right and which is wrong, or which leader was better than another; but merely an attempt to explore what we can learn from a particular exemplar.
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Historians point to the many progressive leadership qualities displayed by Moshoeshoe which he used effectively in establishing the Basotho nation and in defending it.
First, there is his humanism and sense of justice worthy of any great statesman. Confronted by a situation in which cannibals murdered and devoured his grandfather, Moshoeshoe chose not to take revenge. Instead he opted to rehabilitate them and feed them as he believed hunger drove them to cannibalism.

Secondly, there is his skilful alliance-building with his contemporaries such as Shaka in an attempt to neutralize those rivals who were intent on attacking his followers. This is also displayed in the way he sought the protection of the British to keep the Boer forces at bay.
Thirdly, his emphasis on peaceful options is also seen in his defensive military strategy which saw him retreat to a mountain fortress to be able to protect and build a burgeoning nation in the face of the many forces threatening its survival.

Fourthly, there is his remarkable inclusivity and tolerance for diversity which saw him unite disparate groups of refugees from the violence and hunger that displaced them and then weld them into the Basotho nation. He also engaged with French missionaries, inviting them to stay with him and advise him on Western thought, technology and religion.
These are but some of the qualities which belie the notion that all 19th century African leaders were merely marauders and conquerors that gained their ascendancy through violence. Instead Moshoeshoe is a prime example of the human-centred, democratic and pluralist roots of South African, indeed African society.

The Moshoeshoe project that we have initiated (of which the documentary, called “The Renaissance King”, forms but one part) derives from our location as a university in the Free State, a province with a particular history and a particular political culture that developed as a result of this very model of leadership. This province has benefited tremendously from leaders such as Moshoeshoe and president MT Steyn, both of whom many observers credit with establishing a climate of tolerance, respect for diversity of opinion, political accommodation and peaceful methods of pursuing political objectives in the province. Their legacy is real – and Moshoeshoe’s role can not be overstated.
In addition the project derives from the University of the Free State being a site of higher learning in a broader geo-political sense. As a university in Africa we are called upon to understand and critically engage with this history, this context and this legacy.
Besides the documentary, the UFS is also planning to establish an annual Moshoeshoe memorial lecture which will focus on and interrogate models of African leadership, nation-building, reconciliation, diversity management and political tolerance.

In tackling such projects, there may be a temptation to engage in myth-making. It is a trap we must be wary of, especially as an institution of higher learning. We need to ask critical questions about some aspects of Moshoeshoe’s leadership but of current political leadership as well. Thus there is a need for rigorous academic research into aspects of the Moshoeshoe legacy in particular but also into these above-mentioned issues.
While the documentary was commissioned to coincide with the University of the Free State’s centenary and our country’s ten years of democracy, it is a project that has a much wider significance. It is an attempt to get people talking about our past and about our future, as a campus, as a province and as a country – even as a continent, given the NEPAD initiatives to promote democracy and good governance.

The project therefore has particular relevance for the continued transformation of institutions such as universities and the transformation of our society. Hopefully it will assist those who are confronted by the question how to bring about new institutional cultures or even a national political culture that is truly inclusive, tolerant, democratic, non-sexist, non-racial, multilingual and multicultural.

I believe that the Moshoeshoe model of leadership can be emulated and provide some point of convergence. A fractured society such as ours needs points of convergence, icons and heroes which we can share. Moshoeshoe is one such an African icon – in a world with too few of them.

Prof Frederick Fourie is the Rector and Vice-Chancellor of the University of the Free State

* The documentary on “Moshoeshoe: The Renaissance King” will be screened on SABC2 on 4 November 2004 at 21:00.

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