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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

Letter to students from Prof Jonathan Jansen about student protest action at the UFS

2015-10-21

Dear Students

Student protest action at the University of the Free State

I wish to make clear that the senior leadership of the University of the Free State understands and supports the demands from students and their leaders that higher education be accessible to all students, especially the poor. For the past six years we have done everything in our power to meet that commitment to students who are academically talented, but simply cannot afford to pay; that is why our tuition fees remain among the lowest in the country. Our efforts to raise private funding have enabled thousands more students to study at the UFS than would have been possible on the government subsidy only. Whether it is the Staff Fund contributions (yes, our staff empty their pockets to support student fees) or the No Student Hungry (NSH) bursary programme (yes, we raise funds for food bursaries), we will continue our drive to fund students who cannot afford higher education. Let me repeat, no student with a solid academic record will be denied access to studies simply because they cannot pay.

Now, to the matter at hand. There is a national demand from students for a 0% fee increment for 2016. The Minister’s response, after consultation with stakeholders, was that universities should cap their 2016 fee increases at 6%. Despite this initiative from government, the protests continue on virtually all campuses across South Africa for the ‘no fee’ increase.

Our response, as the UFS leadership, is to continue engaging the SRC as the chosen leadership of our students in trying to negotiate a settlement on the matter. We have worked around the clock to be available to student leaders to find some resolution on 2016 fees. While we understand the demands of students, as university leaders, we can only work with the government subsidy we receive. Any agreement reached, cannot and must not place the university at academic and financial risk in its ability to deliver public higher education to the country - if that happens, everybody loses. Still, no matter what happens in terms of the response from government, the leadership door at the UFS remains open to finding a mutually acceptable solution to all parties in these deliberations.

Students, we are deeply concerned by the violence, intimidation and threats from the small group of protesting students. These dangerous and demeaning behaviours, like disrupting classes and verbally abusing students and staff, undermine the legitimate quest of students for relief concerning tuition fees. Such behaviour is completely unacceptable and the university will take action where required. We must also remember that we have an obligation to all 30 000 students whose right to learn without fear of violence and intimidation must be respected.

In conclusion, over the past few years we have worked hard to build a culture of mutual respect and embrace as we worked through some very difficult challenges on campus. You would have noticed that the university leadership responded quickly and sympathetically to reason and respect in difficult situations of rage and demonstration. A minority of students, with some outsiders, have come onto the campus to break down that culture in which, while we might disagree, we continue to work on the basis of mutual respect. I urge all students that, as we engage of this important problem of enabling greater access to higher education, we continue to remain true to the core values of our Human Project.

Best Regards

Prof Jonathan Jansen
Vice-Chancellor and Rector
University of the Free State

Letter to students from Prof Jonathan Jansen about student protest actions at the UFS (Pdf format)

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