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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

Researcher part of project aimed at producing third-generation biofuels from microalgae in Germany

2016-05-09

Some of the researchers and technicians among the tubes of the Novagreen bioreactor (Prof Grobbelaar on left)

A researcher from the University of the Free State (UFS), Prof Johan Grobbelaar, was invited to join a group of scientists recently at the Institute for Bio- and Geo-Sciences of the Research Centre Jülich, in Germany, where microalgae are used for lipid (oil) production, and then converted to kerosene for the aviation industry.

The project is probably the first of its kind to address bio-fuel production from microalgae on such a large scale.

“The potential of algae as a fuel source is undisputed, because it was these photoautotrophic micro-organisms that were fixing sunlight energy into lipids for millions of years, generating the petroleum reserves that modern human civilisation uses today. However, these reserves are finite, so the challenge is marrying biology with technology to produce economically-competitive fuels without harming the environment and compromising our food security. The fundamental ability that microalgae have to produce energy-rich biomass from CO2, nutrients, and sunlight through photosynthesis for biofuels, is commonly referred to as the Third-Generation Biofuels (3G),” said Prof Grobbelaar.

The key compounds used for bio-diesel and kerosene production are the lipids and, more particularly, the triacylglyserols commonly referred to as TAGs. These lipids, once extracted, need to be trans-esterified for biodiesel, while a further “cracking” step is required to produce kerosene. Microalgae can store energy as lipids and/or carbohydrates. However, for biofuels, microalgae with high TAG contents are required. A number of such algae have been isolated, and lipid contents of up to 60% have been achieved.

According to Prof Grobbelaar, the challenge is large-scale, high-volume production, since it is easy to manipulate growth conditions in the laboratory for experimental purposes.

The AUFWIND project (AUFWIND, a German term for up-current, or new impetus) in Germany consists of three different commercially-available photobioreactor types, which are being compared for lipid production.

Manipulated Chlorella with high lipid contents (yellow) in the Novagreen bioreactor

The photobioreactors each occupies 500 m2 of land surface area, are situated next to one another, and can be monitored continuously. The three systems are from Novagreen, IGV, and Phytolutions. The Novagreen photobioreactor is housed in a glass house, and consist of interconnected vertical plastic tubes roughly 150 mm in diameter. The Phytolutions system is outdoors, and consists of curtains of vertical plastic tubes with a diameter of about 90 mm. The most ambitious photobioreactor is from IGV, and consists of horizontally-layered nets housed in a plastic growth hall, where the algae are sprayed over the nets, and allowed to grow while dripping from one net to the next.

Prof Grobbelaar’s main task was to manipulate growth conditions in such a way that the microalgae converted their stored energy into lipids, and to establish protocols to run the various photobioreactors. This was accomplished in just over two months of intensive experimentation, and included modifications to the designs of the photobioreactors, the microalgal strain selection, and the replacement of the nutrient broth with a so-called balanced one.

Prof Grobbelaar has no illusions regarding the economic feasibility of the project. However, with continued research, optimisation, and utilisation of waste resources, it is highly likely that the first long-haul flights using microalgal-derived kerosene will be possible in the not-too-distant future.

Prof Grobbelaar from the Department of Plant Sciences, although partly retired, still serves on the editorial boards of several journals. He is also involved with the examining of PhDs, many of them from abroad. In addition, he assisted the Technology Innovation Agency of South Africa in the formulation of an algae-biotechnology and training centre. “The chances are good that such a centre will be established in Upington, in the Northern Cape,” Prof Grobbelaar said.

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