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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

Protection of Information bill- opinions from our experts

2011-11-28

Prof. Hussein Solomon
Senior Professor in the Department of Political Science at the University of the Free State.

In recent years, given their failure to effectively govern, the ANC has become increasingly defensive. These defensive traits have become particularly acute in light of the various corruption scandals that members of the ruling party involve themselves in.

Given the fact that for now they are assured of an electoral majority (largely on account of their anti-apartheid credentials), coupled with the fact that they have managed to make parliament a rubber stamp of the executive as opposed to holding the executive accountable, it is the media which has increasingly held the ruling party to account by exposing such corruption and incompetence in government.

The passing of the information bill, therefore, is not merely an attack on the media, but an attack on the pivotal issue of accountability. Without accountability, there can be no democracy.

By defining national interest broadly, by refusing to accept a public interest clause in the bill, the ANC increasingly shows its disdain to South Africa's constitution and its citizens.

More importantly, as former Minister of Intelligence and ANC stalwart Ronnie Kasrils pointedly makes clear, the ANC is also betraying its own noble struggle against the odious apartheid regime. It was the media which played a key role in exposing apartheid's excesses, it is the same media which is coming under attack by the heirs of PW Botha's State Security Council - Minister of State Security Siyabong Cwele and his security apparatchiks whose mindsets reflect more Stalin's Gulag's than the values of the Freedom Charter.

The passing of this bill is also taking place at a time when journalists have had their phones attacked, where the judiciary has been deliberately undermined and parliament silenced.

Democrats beware!

Prof. Johann de Wet

Chairperson: Department of Communication Science

The ANC’s insistence on passing the Protection of State Information Bill in its current form and enforcing it by law, means that the essence of our democratic state and the quality of life of every citizen is at stake.

Yes, our freedom as academics, researchers, mass media practitioners and citizens comes into play. Freedom implies the right to choose and is, along with equality, an underlying principle which helps make democracy happen. While the South African state needs to protect (classify) information which could threaten its security and/or survival, the omission of a public interest clause in the Bill at this stage effectively denies a citizen the right to freedom of information.

Freedom of information, along with press freedom, freedom of speech, freedom of assembly, freedom of association and religious freedom, are essential to democracy. These freedoms are granted because they conform to basic liberal ideas associated with (Western) democracy and which resonate with South Africa’s liberal constitution, such as (1) belief in the supreme value of the individual (and thus not of the state); (2) belief that the individual has natural rights (rights which belong to all human beings by nature – such as the right to life and to control government)) which exist independently of government, and which ought to be protected by and against government; and (3) recognition of the supreme value of the individual.

One wonders how many cases of South African government corruption and mismanagement would have been uncovered by investigative journalists over the past number of years if this Bill in its current form was on the statute books. This Bill represents a backward step from the promise of democracy of having an informed public. The former National Party government had similar laws in place and one does not want to go there again. The infamous Information Scandal in South Africa of some thirty years ago, or Muldergate as it has come to be known, reminds one of what governments can do when it works clandestinely.

What South Africans need, is more information on what government structures are doing and how they are doing it with taxpayers’ money, not less information. While information in itself does not equal communication or dialogue, it is an indispensable part thereof, and the need for dialogue based on verifiable information is urgent for meeting vexed challenges facing South African communities. Academics in all fields of specialisation are constantly in need of untainted information to pursue answers and/or offer solutions to where South Africa should be moving in all spheres of life.

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