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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

Moshoeshoe film screened at UFS as part of transformation programme

2004-10-14

A ground-breaking documentary film on the life and legacy of King Moshoeshoe I, the founder of the Basotho nation, will be screened at the University of the Free State (UFS) tonight (Wednesday 13 October 2004) at 19:00.

Rector and Vice-Chancellor of the UFS, prof. Frederick Fourie, said the UFS commissioned the documentary as a practical demonstration of the university’s commitment to the continued transformation of the campus and the creation of a new inclusive institutional culture for all staff and students.

It is part of a larger UFS project to honour the Moshoeshoe legacy of nation-building and reconciliation and to explore his role as a model of African leadership.

The documentary tells the life story of the legendary king, with emphasis on his remarkable leadership skills, his extraordinary talent for diplomacy and conflict resolution and his visionary commitment to creating a new nation from a fragmented society.

Almost all the filming was done on or around Moshoeshoe’s mountain stronghold, Thaba Bosiu.

The last part of the documentary explores the lessons for African leadership to be learnt from Moshoeshoe. The hour-long documentary film was produced by the well-known journalist Mr Max du Preez and was commissioned by the UFS as part of its centenary celebrations.

“Through this documentary film about King Moshoeshoe, the UFS commits itself to developing a shared appreciation of the history of this country,” said prof. Fourie.

“King Moshoeshoe was a great African statesman and leader. He was born in this region of the country, but his influence and legacy extends way beyond the borders of the Free State, Lesotho and even way beyond the borders of South Africa,” said prof. Fourie.

As part of the larger project, the UFS is investigating a possible annual Moshoeshoe memorial lecture that will focus on African leadership, nation-building and reconciliation, possible PhD-level research into the life and legacy of King Moshoeshoe and a literary anthology including prose and poetry.

“We must gain a deeper understanding of what really happened during his reign as king. Therefore the University of the Free State will encourage and support further research into the history, politics and sociology of the Moshoeshoe period, including his leadership style,” said prof. Fourie.

According to prof. Fourie the Moshoeshoe project will enable the UFS to give real meaning to respect for the diversity of our languages and cultures, and the unity South Africans seek to build as a democratic nation through such diversity.

According to the producer of the documentary, journalist Mr Max du Preez, the UFS deserves credit for recognising this extraordinary man and for financing this important documentary.

Du Preez said: “It was about time that South Africa rediscovered Moshoeshoe. Colonialist and Afrikaner Nationalist historians have painted him as a sly, untrustworthy and weak leader. Most historians have preferred to glorify leaders in South Africa’s past who were aggressors and conquerors. In the process most present-day South Africans came to regard Moshoeshoe as a minor tribal figure.”

“Yet this was the man who broke the cycle of violence, famine and suffering during the traumatic time in central South Africa in the early 1800s. During the entire 19th century, Moshoeshoe was virtually the only leader in South Africa who did not answer violence with violence, who did not set forth to conquer other groups and expand his land,” said Mr du Preez.

“I have no doubt that the stability that the Free State region has enjoyed over more than a century was largely due to Moshoeshoe’s leadership and vision. He can quite rightly be called “The Nelson Mandela of the 19th Century,” Mr du Preez added.

Explaining the title of the documentary film, Mr du Preez said: “We decided to call the documentary “The Reniassance King” because whichever way one looks at it, Moshoeshoe symbolised everything behind the concept of an African Renaissance.”

“He was progressive, just and fair; he deeply respected human life and dignity (we would nowadays call it human rights); he embraced modernity and technology without ever undermining his own people’s culture or natural wisdom; he never allowed European or Western influence to overwhelm him, make him insecure or take away his pride as an African,” said Mr du Preez.

“Moshoeshoe was the best of Africa. If only contemporary African leaders would follow his example of what African leadership should be,” Mr du Preez said.

Among the interviewees in the film were Lesotho’s most prominent historian, Dr LBBJ Machobane, the head of the UFS’s Department of History, prof. Leo Barnard, Moshoeshoe expert and Gauteng educationist Dr Peter Seboni, Lesotho author and historian Martin Lelimo and Chief Seeiso Bereng Seeiso, Principal Chief of Matsieng and direct descendant of the first King of the Basotho.

The documentary film on King Moshoeshoe will be screened on SABC 2 on Thursday 4 November 2004.

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