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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

Academic and security arrangements on the Bloemfontein and South Campuses for the coming week

2016-02-28

All academic and administrative services on the Bloemfontein and South Campuses of the University of the Free State (UFS) will resume on Monday 29 February 2016.

The following academic and security arrangements have been put in place:

1. Academic arrangements:
It is important to remember that losing an academic week has major implications for all students, particularly for first-year students, and for purposes of academic planning. The university will therefore resume its normal work on Monday 29 February 2016. Losing any additional time will severely disadvantage students, especially those who desperately need the time to catch up with lectures ahead of the coming tests and examinations. Many more students will struggle to complete the academic year if any further time is lost.

In order to ensure that the academic work of the university is not undermined, the UFS will extend this academic term by one week. This will allow the completion of the work scheduled for last week. Given the impact that disruptions had on the emotions and concentration of many of our students, academics are requested to manage the setting and re-setting of all tests and assignments scheduled for last week with sensitivity, and to be supportive of students as they re-start their academic work. No student should be disadvantaged in terms of tests or assignments as a result of last week’s closure. We know you would do this anyway, but this is a reminder to all staff of what we expect to be a common approach and understanding on the part of lecturers.

We rely on the leadership of the deans in the seven faculties to support staff and students in dealing with the lost time in the most appropriate manner and in supporting all efforts to refocus energies on the academic project.

As the senior leadership and management of the university, we will continue to do everything in our power to make sure that the academic programme continues uninterrupted.

2. Security arrangements:
The Bloemfontein Campus is secure and we have more than doubled the security arrangements, with the interdict firmly in place.

The university management condemns in the strongest possible terms the violence that took place at Xerox Shimla Park on the night of Monday 22 February 2016. It also condemns the disruptions of the university that followed Monday’s event, which resulted in the suspension of academic and administrative activities on the Bloemfontein Campus. In line with the terms of the interdict - and now that we are at full capacity to secure this very large and spread-out campus - the university will act swiftly and firmly if any protests or disruption recur.

The following security arrangements are in place:
2.1 Staff and students must have their staff and student cards with them when entering the campus. Passengers in motor vehicles will have to present their cards to security personnel before access could be granted. Security personnel will check this physically by verifying that each person has a valid staff or student card.

2.2 Buses will not be allowed to enter the campus and passengers will have to be dropped off outside the gates - passengers will enter through the turnstiles with their valid access cards. Anyone without a valid access card will have to go to the Visitors Centre and present positive proof of ID (SA ID, passport or driver’s licence).

2.3 Pedestrians will have to swipe their cards at the turnstiles at the gates. Those without cards will have to enter through the Visitors Centre by presenting positive proof of ID (SA ID, passport or driver’s licence).

2.4 Visitors must report to the Visitors Centre (at Gate 5 in DF Malherbe Drive) and present positive proof of ID (SA ID, passport or driver’s licence).

2.5 Due to anticipated delays, it is advised that people allow some additional time when planning their routes to campus and to also make use of the less busy gates, such as Gate 4 (Furstenburg Road) and Gate 2 (Roosmaryn Residence).

2.6 It is advised that walkways be used, especially at night, and that pedestrians should keep to areas that are well lit.

Security helpline: +27(0)51 401 2911 | +27(0)51 401 2634.

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