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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

Bloemfontein's quality of tap water compares very favourably with bottled water

2009-08-04

The quality of the drinking water of five suburbs in Bloemfontein is at least as good as or better than bottled water. This is the result of a standard and chemical bacterial analysis done by the University of the Free State’s (UFS) Centre for Environmental Management in collaboration with the Institute for Groundwater Studies (IGS).

Five samples were taken from tap water sources in the suburbs of Universitas, Brandwag, Bain’s Vlei, Langenhoven Park and Bayswater and 15 samples were taken of different brands of still and unflavoured bottled water. The samples were analysed at the laboratory of the IGS, while the interpretation of the analysis was done by the Centre for Environmental Management.

“We wanted to evaluate the difference in quality for human consumption between tap water and that of the different brands of bottled water,” said Prof. Maitland Seaman, Head of the Centre for Environmental Management.

“With the exception of two samples produced by multinational companies at their plants in South Africa, the different brands of bottled water used for the study were produced by South African companies, including a local small-scale Bloemfontein producer,” said Prof. Seaman.

According to the labels, the sources of the water vary from pure spring water, to partial reverse osmosis (as an aid to standardise salt, i.e. mineral, content), to only reverse osmosis (to remove salts). (Reverse osmosis is a process in which water is forced under pressure through a pipe with minute pores through which water passes but no – or very low concentrations of – salts pass.)

According to Prof. Seaman, the analysis revealed some interesting findings, such as:

• It is generally accepted that drinking water should have an acceptable level of salt content, as the body needs salts. Most mineral contents were relatively higher in the tap water samples than the bottled water samples and were very much within the acceptable range of drinkable water quality. One of the bottled samples, however, had a very low mineral content, as the water was produced by reverse osmosis, as stated on the bottle. While reverse osmosis is used by various producers, most producers use it as an aid, not as a single method to remove nearly all the salts. Drinking only such water over a prolonged period may probably have a negative effect on the human physiology.

• The pH values of the tap water samples (8,12–8,40) were found to be slightly higher (slightly alkaline), like in all south-eastern Free State rivers (from where the water is sourced) than the pH of most of the bottled water samples, most of which are sourced and/or treated in other areas. Two brands of bottled water were found to have relatively low pH levels (both 4,5, i.e. acidic) as indicated on their bottles and as confirmed by the IGS analysis. The health implication of this range of pH is not significant.

• The analysis showed differences in the mineral content given on the labels of most of the water bottles compared to that found by IGS analysis. The possibility of seasonal fluctuation in content, depending on various factors, is expected and most of the bottling companies also indicate this on their labels. What was a rather interesting finding was that two pairs of bottled water brands claimed exactly the same mineral content but appeared under different brand names and were also priced differently. In each case, one of the pair was a well-known house brand, and the other obviously the original producer. In one of these paired cases, the house brand stated that the water was spring water, while the other (identical) “original” brand stated that it was spring water treated by reverse osmosis and oxygen-enriched.

• Nitrate (NO3) levels were uniformly low except in one bottled sample, suggesting a low (non-threatening) level of organic pollution in the source water. Otherwise, none of the water showed any sign of pollution.

• The bacterial analysis confirmed the absence of any traces of coliforms or E.coli in any of the samples, as was also indicated by the bottling companies. This is very reassuring. What is not known is how all these waters were sterilised, which could be anything from irradiation to chlorine or ozone treatment.

• The price of the different brands of bottled water, each containing 500 ml of still water, ranged between R3,99 and R8,99, with R5,03 being the average price. A comparison between the least expensive and the most expensive bottles of water indicated no significant difference in quality. In fact, discrepancies were observed in the most expensive bottle in that the amount of Calcium (Ca) claimed to be present in it was found to be significantly different from what the analysis indicated (29,6 mg/l versus 0,92 mg/l). The alkalinity (CaCO3 mg/l) indicated on the bottle was also found to differ considerably (83 mg/l versus 9,4 mg/l). The concentration of Total Dissolved Salts (TDS) was not given on the product.

“The preference for bottled water as compared to Bloemfontein’s tap water from a qualitative perspective as well as the price discrepancy is unjustifiable. The environmental footprint of bottled water is also large. Sourcing, treating, bottling, packaging and transporting, to mention but a few of the steps involved in the processing of bottled water, entail a huge carbon footprint, as well as a large water footprint, because it also requires water for treating and rinsing to process bottled water,” said Prof. Seaman.

Media Release
Lacea Loader
Deputy Director: Media Liaison
Tel: 051 401 2584
Cell: 083 645 2454
E-mail: loaderl.stg@ufs.ac.za
3 August 2009

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