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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 forgive is not an obligation. It’s a choice.” – Prof Minow during Reconciliation Lecture

2014-03-05

“To forgive is not an obligation. It’s a choice.” – Prof Minow during the Third Annual Reconciliation Lecture entitled Forgiveness, Law and Justice.
Photo: Johan Roux

No one could have anticipated the atmosphere in which Prof Martha Minow would visit the Bloemfontein Campus. And no one could have predicted how apt the timing of her message would be. As this formidable Dean of Harvard University’s Law School stepped behind the podium, a latent tension edged through the crowded audience.

“The issue of getting along after conflict is urgent.”

With these few words, Prof Minow exposed the essence of not only her lecture, but also the central concern of the entire university community.

As an expert on issues surrounding racial justice, Prof Minow has worked across the globe in post-conflict societies. How can we prevent atrocities from happening? she asked. Her answer was an honest, “I don’t know.” What she is certain of, on the other hand, is that the usual practice of either silence or retribution does not work. “I think that silence produces rage – understandably – and retribution produces the cycle of violence. Rather than ignoring what happens, rather than retribution, it would be good to reach for something more.” This is where reconciliation comes in.

Prof Minow put forward the idea that forgiveness should accompany reconciliation efforts. She defined forgiveness as a conscious, deliberate decision to forego rightful grounds of resentment towards those who have committed a wrong. “To forgive then, in this definition, is not an obligation. It’s a choice. And it’s held by the one who was harmed,” she explained.

Letting go of resentment cannot be forced – not even by the law. What the law can do, though, is either to encourage or discourage forgiveness. Prof Minow showed how the law can construct adversarial processes that render forgiveness less likely, when indeed its intention was the opposite. “Or, law can give people chances to meet together in spaces where they may apologise and they may forgive,” she continued. This point introduced some surprising revelations about our Truth and Reconciliation Commission (TRC).

Indeed, studies do report ambivalence, disappointment and mixed views about the TRC. Whatever our views are on its success, Prof Minow reported that people across the world wonder how South African did it. “It may not work entirely inside the country; outside the country it’s had a huge effect. It’s a touchstone for transitional justice.”

The TRC “seems to have coincided with, and maybe contributed to, the relatively peaceful political transition to democracy that is, frankly, an absolute miracle.” What came as a surprise to many is this: the fact that the TRC has affected transitional justice efforts in forty jurisdictions, including Rwanda, Sierra Leone, Cambodia and Liberia. It has even inspired the creation of a TRC in Greensborough, North Carolina, in the United States.

There are no blueprints for solving conflict, though. “But the possibility of something other than criminal trials, something other than war, something other than silence – that’s why the TRC, I think, has been such an exemplar to the world,” she commended.

Court decision cannot rebuild a society, though. Only individuals can forgive. Only individuals can start with purposeful, daily decisions to forgive and forge a common future. Forgiveness is rather like kindness, she suggested. It’s a resource without limits. It’s not scarce like water or money. It’s within our reach. But if it’s forced, it’s not forgiveness.

“It is good,” Prof Minow warned, “to be cautious about the use of law to deliberately shape or manipulate the feelings of any individual. But it is no less important to admit that law does affect human beings, not just in its results, but in its process.” And then we must take responsibility for how we use that law.

“A government can judge, but only people can forgive.” As Prof Minow’s words lingered, the air suddenly seemed a bit more buoyant.

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