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Archive for September, 2024

Lessons from the lab: Using human brain tissue to study astroglia

By e.wylde, on 25 September 2024

In this blog, Dr Olga Tiurikova, Research Fellow in the Department of Clinical & Experimental Epilepsy at the UCL Queen Square Institute of Neurology talks about the benefits and challenges of using human brain tissue in research. 

One of the current ethical challenges in sustainable research is finding feasible alternatives for the use of animals in laboratory experiments. That’s why I was excited to participate in a study funded by the NC3Rs (National Centre for the Replacement, Refinement, and Reduction of Animals in Research). Working with a team led by Prof. Dmitri Ruskov and Prof. Matthew Walker, we used human brain tissue removed during epilepsy surgeries to study astroglia. Astroglia are a class of neural cells that are foung in the brain and spinal cord. They support neurons, repair damage, and maintain the blood-brain barrier. This research, in collaboration with neurosurgeons from Queen Square Hospital and the Cleveland Clinic, allowed us to explore how these cells function and respond to physiological stimuli. Here, I want to share the key lessons learned—the benefits and challenges of using human brain tissue in research—hoping to inspire others to consider similar approaches.

Why human brain tissue for glial research?

Astroglia, once thought to be merely structural support cells, are now recognised as active players in brain function. They shape synaptic transmission and are seen as key targets for treating neurological disorders. Over the years, many attempts have been made to study the properties of human astroglial cells, mostly using fixed post-mortem human brain samples. Whilst useful for morphological studies, fixed samples are useless for understanding how live astroglia work. That’s where our project comes in—we use human brain tissue immediately after surgery to keep cells alive and study these cells in action.

The unique benefits of using human brain tissue

While the use of animal models remains invaluable in advancing our understanding of cellular mechanisms, they fall short of capturing the full complexity of human biology. This gap is particularly evident in studies of astroglia. For instance, the human cortex contains five distinct subtypes of astroglia, two of which are absent in rodents. These astroglial subtypes have unique, long, cable-like protrusions spanning multiple layers of the cortex, however, their functions remain largely unknown. Thus, using human brain tissue opens new possibilities to study these subtypes of astroglia that may be missed when relying solely on animal models and lead to new therapeutic opportunities.

That said, animal research is still crucial for studying complex systems, especially in the context of diseases and treatments. The real strength lies in integrating both approaches: using human tissue to investigate cellular processes and animal models to explore how new findings translate into the systemic level for long-term effects.

Navigating the challenges

Despite its promise, working with human brain tissue comes with challenges. One of the biggest hurdles was the time-sensitive nature of the samples. Since the tissue had to be studied within hours after removal, we ensured all experimental settings were ready before the surgery even began. The occasional nature of experiments requires us to be extremely efficient. To mitigate some obstacles, we are considering creating organotypic human tissue. This miniaturized, lab-grown brain tissue—or organotypic cultures we can apply to extend the usability of such a valuable post-surgical human sample.

Towards a more ethical future

Using human brain tissue from surgeries marks a significant step forward in reducing animal testing in neuroscience. This approach enhances our understanding of human brain function. Moreover, it aligns with ethical research practices and reduces the number of animals used. While animal models will remain essential for some studies, human brain tissue offers a valuable alternative, helping us move toward more humane and effective research methodologies.

 

Image credit: Google DeepMind on Pexels