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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

To tan or not to tan: a burning issue

2009-12-08

Prof. Werner Sinclair

“Some evidence exists which implies that sunscreens could indeed be responsible for the dramatic rise in the incidence of melanoma over the past three decades, the period during which the use of sunscreens became very popular,” says Prof. Werner Sinclair, Head of the Department of Dermatology at the University of the Free State. His inaugural lecture was on the topic Sunscreens – Curse or Blessing?

Prof. Sinclair says the use of sunscreen preparations is widely advocated as a measure to prevent acute sunburn, chronic sun damage and resultant premature skin aging as well as skin malignancies, including malignant melanoma. There is inconclusive evidence to prove that these preparations do indeed achieve all of these claims. The question is whether these preparations are doing more harm than good?

He says the incidence of skin cancer is rising dramatically and these tumours are induced mostly by the ultra-violet rays.

Of the UV light that reaches the earth 90-95% belongs to the UVA fraction. UVC is normally filtered out by the ozone layer. UVB leads to sunburn while UVA leads to pigmentation (tanning). Because frequent sunburn was often associated with skin cancer, UVB was assumed, naively, to be the culprit, he says.

Exposure to sunlight induces a sense of well-being, increases the libido, reduces appetite and induces the synthesis of large amounts of vitamin D, an essential nutritional factor. The use of sunscreen creams reduces vitamin D levels and low levels of vitamin D have been associated with breast and colon cancer. Prof. Sinclair says the 17% increase in breast cancer from 1981 to 1991 parallels the vigorous use of sunscreens over the same period.

Among the risk factors for the development of tumours are a family history, tendency to freckle, more than three episodes of severe sunburn during childhood, and the use of artificial UV light tanning booths. He says it remains a question whether to tan or not. It was earlier believed that the main carcinogenic rays were UVB and that UVA merely induced a tan. The increase in UVA exposure could have severe consequences.

Prof. Sinclair says the UV light used in artificial tanning booths consists mainly of pure UVA which are highly dangerous rays. It has been estimated that six per cent of all melanoma deaths in the UK can be directly attributed to the use of artificial tanning lights. The use of an artificial tanning booth will double the melanoma risk of a person. “UVA is solely responsible for solar skin aging and it is ironical that tanning addicts, who want to look beautiful, are inflicting accelerated ageing in the process,” he says.

On the use of sunscreens he says it can prevent painful sunburn, but UVA-induced damage continues unnoticed. UVB blockers decrease vitamin D synthesis, which is a particular problem in the elderly. It also prevents the sunburn warning and therefore increases the UVA dosage that an individual receives. It creates a false sense of security which is the biggest problem associated with sunscreens.

Evidence obtained from the state of Queensland in Australia, where the heaviest and longest use of sunscreens occurred, boasted the highest incidence of melanoma in the world. A huge study in Norway has shown a 350% increase in melanoma for men and 440% for women. This paralleled the increase in the use of UVB blocking sunscreens while there was no change in the ozone layer. It did however, occur during that time when tanning became fashionable in Norway and there was an increase especially in artificial tanning.

Prof. Sinclair says: “We believe that sunscreen use does not directly lead to melanoma, but UVA exposure does. The Melanoma Epidemic is a reality. Sunscreen preparations are not the magical answer in the fight against melanoma and the irresponsible use of these preparations can worsen the problem.”

Media Release
Issued by: Mangaliso Radebe
Assistant Director: Media Liaison
Tel: 051 401 2828
Cell: 078 460 3320
E-mail: radebemt.stg@ufs.ac.za
7 December 2009

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