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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

Weideman focuses on misconceptions with regard to survival of Afrikaans

2006-05-19

From the left are Prof Magda Fourie (Vice-Rector: Academic Planning), Prof Gerhardt de Klerk (Dean: Faculty of the Humanities), George Weideman and Prof Bernard Odendaal (acting head of the UFS Department of Afrikaans and Dutch, German and French).
Photo (Stephen Collett):

Weideman focuses on misconceptions with regard to survival of Afrikaans

On the survival of a language a persistent and widespread misconception exists that a “language will survive as long as people speak the language”. This argument ignores the higher functions of a language and leaves no room for the personal and historic meaning of a language, said the writer George Weideman.

He delivered the D.F. Malherbe Memorial Lecture organised by the Department Afrikaans at the University of the Free State (UFS). Dr. Weideman is a retired lecturer and now full-time writer. In his lecture on the writer’s role and responsibility with regard to language, he also focused on the language debate at the University of Stellenbosch (US).

He said the “as-long-as-it-is spoken” misconception ignores the characteristics and growth of literature and other cultural phenomena. Constitutional protection is also not a guarantee. It will not stop a language of being reduced to a colloquial language in which the non-standard form will be elevated to the norm. A language only grows when it standard form is enriched by non-standard forms; not when its standard form withers. The growth or deterioration of a language is seen in the growth or decline in its use in higher functions. The less functions a language has, the smaller its chance to survive.

He said Afrikaans speaking people are credulous and have misplaced trust. It shows in their uncritical attitude with regard to the shifts in university policies, university management and teaching practices. Afrikaners have this credulity perhaps because they were spoilt by white supremacy, or because the political liberation process did not free them from a naïve and slavish trust in government.

If we accept that a university is a kind of barometer for the position of a language, then the institutionalised second placing of Afrikaans at most tertiary institutions is not a good sign for the language, he said.

An additional problem is the multiplying effect with, for instance, education students. If there is no need for Afrikaans in schools, there will also be no need for Afrikaans at universities, and visa versa.

The tolerance factor of Afrikaans speaking people is for some reasons remarkably high with regard to other languages – and more specifically English. With many Afrikaans speaking people in the post-apartheid era it can be ascribed to their guilt about Afrikaans. With some coloured and mostly black Afrikaans speaking people it can be ascribed to the continued rejection of Afrikaans because of its negative connotation with apartheid – even when Afrikaans is the home language of a large segment of the previously oppressed population.

He said no one disputes the fact that universities play a changing role in a transformed society. The principle of “friendliness” towards other languages does not apply the other way round. It is general knowledge that Afrikaans is, besides isiZulu and isiXhosa, the language most spoken by South Africans.

It is typical of an imperialistic approach that the campaigners for a language will be accused of emotional involvement, of sentimentality, of longing for bygone days, of an unwillingness to focus on the future, he said.

He said whoever ignores the emotional aspect of a language, knows nothing about a language. To ignore the emotional connection with a language, leads to another misconception: That the world will be a better place without conflict if the so-called “small languages” disappear because “nationalism” and “language nationalism” often move closely together. This is one of the main reasons why Afrikaans speaking people are still very passive with regard to the Anglicising process: They are not “immune” to the broad influence that promotes English.

It is left to those who use Afrikaans to fight for the language. This must not take place in isolation. Writers and publishers must find more ways to promote Afrikaans.

Some universities took the road to Anglicision: the US and University of Pretoria need to be referred to, while there is still a future for Afrikaans at the Northwest University and the UFS with its parallel-medium policies. Continued debate is necessary.

It is unpreventable that the protest over what is happening to Afrikaans and the broad Afrikaans speaking community must take on a stronger form, he said.

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