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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

Open letter from Prof Jonathan Jansen to all UFS students

2014-02-22

Dear Students of the University of the Free State

In the past four years there has emerged a new consensus on the three campuses of the University of the Free State (UFS) about the things that divide us – such as racism, sexism and homophobia. Students and campus leaders have worked hard to develop this new consensus in residences and in the open spaces on campus. There can be no doubt that new bonds of friendship have developed across the markers of race, ethnicity, class, religion and sexual orientation. I bear witness to these new solidarities every day on the campus.

You chose a white student to head up the transformation portfolio on the SRC. You chose a black captain to head up the university’s first team in rugby. You chose a white “prime” as head of residence to lead a predominantly black men’s residence. You chose a South African woman of Indian descent as Rag Queen and last week, a black student from Cape Town as the men’s Rag winner—choices not possible and never made before in our campus history. Many of you have intimate friends who come from different social or cultural or religious backgrounds. You learn together, share rooms together, pray together and party together. In other words, in the day to day workings of this university campus, you have demonstrated to campus, city and country that we can overcome the lingering effects of racism and other maladies in this new generation. You have helped create a university community inclusive of people of diverse religions, abilities, class and sexual orientation.

I have said this repeatedly that from time to time this new consensus will be tested – when a minority of students, and they are a small and dwindling minority, still act as if these are the days of apartheid. And when that consensus is tested as it was this week, and as it will be tested in the future, only then we will be able to assess the strength and durability of our progress in creating a new South African campus culture of human togetherness based on respect, dignity and embrace.

The real test of our leadership, including student leadership, is how we respond when our transformation drive is threatened.

Let me say this: I have absolute faith in you, as students of this great university, to stand together in your condemnation of these vile acts of violence and to move together in your determination to maintain the momentum for the Human Project of the University of the Free State. We have come too far to allow a few criminals to derail what you have built together in recent years.

There will, no doubt, be unscrupulous people on all sides of the political spectrum wanting to milk this tragedy for their own narrow purposes. There will be false information, rumours and exaggerations by those who wish to inflame a bad situation to gain mileage for their agendas. That is inevitable in a country that is still so divided.

I ask you, through all of this, to keep perspective. Two or ten or even twenty students behaving badly do not represent 30,000 students; a minority of violent and hateful persons do not represent the ideals, ambitions and commitments of the majority. At the same time, let us be realistic – anyone who thinks you can drive transformation without resistance clearly does not understand the difficult process of change.

The events of the week remind us, however, that we still have a long road to walk in deepening social and academic transformation at our university. Yes, we have invested hundreds of hours in training and mentorship; we have created new structures – such as the Institute for Reconciliation and Social Justice – to capture the energy and imagination of students driving transformation; we have created many opportunities for students to study and travel on this and other continents to enable cross-cultural learning; we have established formal and informal opportunities to dialogue about difficult issues on and off campus between students and their leaders; and we crafted new curricula to enable teaching and learning on the big questions of our times.

But this is clearly not enough, and so I have decided on the following immediate next steps:

We will meet for several hours next week to think about how we can deepen the transformation of our university after this terrible incident.
We will arrange a University Assembly on the events of the past week so that we speak with one voice on human wrongs and to re-commit to human rights and we will continue with open forum discussions during the months to come.
We will review the entire spectrum of programmes, from orientation to residence life to the undergraduate curriculum, to determine how effective our interventions really are in reaching all students with respect to basic issues of human rights.
We will review our media and communications strategy to determine how far and deep our messages on human rights travel across all sectors of the university community. In this regard it is important that the campus be blanketed on a regular basis with our condemnation of human wrongs and our commitment to human rights.
We will commission the Institute for Reconciliation and Social Justice to review the events of the past week and make recommendations on how we can improve the campus environment so that all students are protected from harm inside residences, classrooms and in open spaces of the campus.
We will take the questions raised during this week into the academic community and to the general staff of the university so that all personnel also engage with our own roles and responsibilities with respect to campus transformations.
We undertake to make annual report-backs on transformation to all stakeholders in public forums so that students and staff and external communities can track the progress of the university on matters of human rights on campus.

I wish to thank my staff for acting firmly as soon as this tragic event came to our attention. We worked through the night to find and identify the perpetrators. We traced the two students and immediately handed them to the police. They were expelled. And throughout this process we offered counselling and support to the victim of this violent act.

The two former students were expelled and will now face justice in the criminal courts. It is hoped that in the course of time they will come to their senses and seek restoration and reconciliation with the student they so callously harmed. They are not part of the university community anymore.

That is the kind of university we are.

Jonathan D Jansen
Vice-Chancellor and Rector
University of the Free State
20 February 2014

Note: The use of the word ‘campus’ refers to all three campuses of the UFS, namely the Bloemfontein Campus, South Campus and Qwaqwa Campus.

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