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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

Judge Albie Sachs and Candice Mama discuss traumas of the past and forgiveness in the present

2015-08-05

Judge Albie Sachs embraces Candice Mama for her courage in confronting Eugene de Kock, who killed her father.

Two generations. Two stories of triumph. Two South Africans who have displayed immense courage.

Public Dialogue on Trauma, Memory, and Representations of the Past

Judge Albie Sachs and Candice Mama exchanged their experiences of past trauma and subsequent transformation in a public conversation. The event was co-hosted by Prof Pumla Gobodo-Madikizela and The Institute for Justice and Reconciliation (IJR) in Cape Town on Thursday 30 July 2015.

The event was the first instalment in a series entitled Public Dialogue on Trauma, Memory, and Representations of the Past. The theme of the discussion was ‘Intergenerational Dialogue on Trauma and Healing’.

"The aim of these public dialogue events we are co-hosting with IJR is to place the issues of trauma and memory, and the strategies that individuals and communities use to heal, in the public sphere," Prof Gobodo-Madikizela, Senior Research Professor in Trauma, Forgiveness, and Reconciliation Studies at the University of the Free State (UFS) said.

Judge Albie Sachs and Candice Mama in conversation

Former Constitutional Court Judge, Albie Sachs, talked about his participation in South Africa’s liberation struggle, the loss of his right arm in an assassination attempt, and meeting the man responsible – Henri van der Westhuizen. Despite years of exile and extended periods of solitary confinement, Judge Sachs maintains that “we need to acknowledge our history, not be trapped by it.” Judge Sachs also remarked, though, that “we’re seeing too much lamentation, not enough activation.” In a heartrending gesture, Judge Sachs embraced Candice Mama in a hug for her courage in confronting Eugene de Kock, who killed her father.

How poignant then, when Mama said, “I wanted to embrace the brokenness within him,” when she spoke about her meeting with De Kock. By the time I met with Eugene, I could meet him as a human being, not as a villain.” Mama believes that forgiving someone translates into an investment in the person you are forgiving and in your own sanity. She also emphasised the importance of dialogue to move our country forward: “When we share our stories with each other authentically, walls break down.”

This is a stance that Prof Gobodo-Madikizela supports strongly: “When we listen to one another, something unexpected emerges; we encounter the human in each other,” she said. “When we listen with open hearts to each other, we see and experience each other’s humanity.”

Building a bridge between research and society

Referring to the research aspect of the event, Prof Gobodo-Madikizela said that, "in establishing the series of public dialogue events, our vision is to create a bridge between scholarly research and the community at large, on the one hand, and a visual conscience of society, on the other." The UFS is collaborating with the IJR on this research project, which is funded by the Andrew W. Mellon Foundation. The endeavour is led by Prof Gobodo-Madikizela, who also serves as Board Member of the IJR.

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