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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

UFS receives multimillion rand international funding for Advancement

2013-01-21

21 January 2013

We are one of four South African universities that have been selected to take part in a multimillion-rand programme to bolster private fund-raising and Advancement efforts.

The UFS will receive US$640 000 (R5 612 800) over a period of five years to use in advancement efforts.

In total, the US-based Kresge Foundation will make US$2.5 million available to the four universities, which includes the UFS, Durban University of Technology (DUT), Tshwane University of Technology (TUT) and the University of Johannesburg (UJ), over the next five years as part of a joint initiative with Inyathelo: The South African Institute for Advancement, to support the long-term financial sustainability of higher education institutions in South Africa.

Kresge will also provide programmes and support aimed at enhancing student access to universities and improving graduation rates.

Bill Moses, who directs Kresge’s education programme, says declining government support means that South African university officials need to tap into diversified philanthropic and private funding if they want to enhance their institutions’ ability to serve students better. “Stronger Advancement skills are critical to their success and ultimately to getting more South African students into universities and completing degrees. Advancement is not just about raising funds. It is the practice of building, maintaining and improving support, skills and other resources to ensure the sustainability of an institution,” explains Moses.

This latest Kresge initiative follows the success of a five-year partnership with Inyathelo that helped five high-profile South African institutions - the University of the Witwatersrand (Wits); the University of Pretoria (UP); the University of the Western Cape (UWC); the Cape Peninsula University of Technology (CPUT) and the Children’s Hospital Trust - increase their private fund-raising revenue threefold. The four universities will receive additional funding over the next five years and will serve as mentors to the new group of institutions.

In April last year, Kresge announced a new commitment to South African higher education that builds on its efforts in the United States to improve university access and help students succeed academically. Their ‘Promoting access and success at South African universities’ programme will seek to strengthen pathways to and through universities, especially for students who are often unprepared for university study. Moses says enhancing the ability of universities in South Africa to graduate the next generation of knowledge workers, will make it possible for the country to compete more effectively in the global economy. “Access to higher education in South Africa has improved dramatically since the end of Apartheid. A doubling of enrolment since 1994 has, however, contributed to serious challenges, including under-prepared students and disappointing graduation rates. We are confident that our programme will help address some of these obstacles to success,” says Moses.

Kresge has already funded several efforts that support its interest in strengthening pathways to and through universities this year, including a grant to the University of the Free State to expand the South African Survey of Student Engagement, as well as funding to the University of Pretoria to support a conference in January, which will highlight opportunities to promote access and success at South African universities.

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