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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

Workplace discrimination and unfair practices explored in new book

2017-09-13

Dr Denine Smit
Photo: Supplied

Two law scholars, Dr Denine Smit and Dr Damian Viviers, from the Faculty of Law at the University of the Free State (UFS) recently launched a book titled Vulnerable Employees, which was inspired by their interest in researching, creating awareness and providing a legal exposition in relation to employees who are vulnerable and experience prejudice and dignity violations in the workplace. These include workplace bullying, appearance-based discrimination, those who are gender fluid or have mental-health conditions.
“Dr Viviers, who is also a former student of mine, and I, have been working together for years and share a common understanding in relation to our various topics of interest. We often share the same train of thought. This is how we came to work together to produce this book,” said Dr Smit.

Research focused on employee challenges in the workplace
The book expands on the field of knowledge regarding certain categories of employees who, as a consequence of various mutable, immutable and semi-immutable characteristics, as well as behavioural experiences, are rendered vulnerable in their employment relationships. The book draws on various social, psychological and other empirical considerations, as well as comparative legal research from foreign and international law, in order to expand on the legal position under the South African legal framework governing these conditions. While the book first and foremost constitutes a compendium of research to be used for this purpose, it also serves as a practical guide for all legal practitioners, human resources managers, other labour stakeholders and the judiciary.

Book draws strength in other academic fields
Vulnerable Employees was launched on 28 July 2017 at the UFS library, to an audience of academics and students, with a panel discussion made up of the authors and two other panellists. One of the panellists was Dr Katinka Botha, a leading psychiatrist in the Free State who has a wealth of experience in this field. “Her selection as a panellist was motivated by the various significant inter-disciplinary considerations and intersections between psychology, psychiatry and law, contained in the book,” said Dr Smit.
“Dr Botha’s expertise was invaluable in shedding light on mental-health considerations during the panel discussion.”
Mr Lesley Mokgoro, the other panellist, is a leading labour law practitioner, as well as director and head of the Dispute Resolution Practice Group at Phatshoane Henney Attorneys. “His years of experience working with all role players in the employment domain, as well as his extensive legal knowledge and expertise, made him uniquely qualified to serve on the panel and deliver an opinion of the practical and academic value of the book,” said Dr Smit.

Workplace policies key to securing employee rights
There are a number of growing trends in the workplace that could shape the practice of labour law or workplace policies. Dr Smit said the need for employers to regulate workplace culture, particularly in relation to bullying, harassment and unfair discrimination, in line with the South African legal framework, was a fundamental need in all workplaces. Effective workplace policies may be used to clearly outline the relevant “dos and don’ts” to employees, as well as the procedures and processes that may be followed in order to address such conduct. Workplace policies serve to advance legal certainty and efficiency, since the rights and obligations of all role players are clearly demarcated, or should be, in terms of a well-drafted and considered policy.
The book is one of several publications produced by Dr Smit in collaboration with Dr Viviers on the topic of workplace discrimination and the law. The two scholars are working on another book to be published at the end of 2017.

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