New Approach to Studying Neuropathies and Reducing Animal Testing

A new study published in the journal Stem Cells Reports has found that cellular reprogramming techniques, which generate cultures of human neurons using skin cells, could revolutionize the study and development of innovative therapies for neuropathies. This is because the cellular reprogramming methodology creates neural networks that have unique characteristics of human cells, rather than those obtained from rodent cells. The findings of this study could boost not only the development of new therapies for neuropathies but also reduce the use of animal experimentation in laboratories.

The study was led by researcher Daniel Tornero Prieto from the Faculty of Medicine and Health Sciences at the University of Barcelona, as well as researchers from the University of Lund in Sweden. The team utilized cellular reprogramming for their work, which is a technique first developed by Shinya Yamanaka in 2007 involving the induction of human pluripotent stem cells. 

The research team used a technique called intracellular calcium level recordings to compare the properties of neuronal cultures generated with cell reprogramming technology from human cells with those obtained from rodents and human brains. This technique measures neuronal activity by recording the rise in calcium levels during the transmission of nerve impulses from one neuron to the next.

For the first time, the research team studied and differentiated the characteristics of the different neural circuits generated, finding that human neurons behave differently when generating functional neural circuits. These characteristics may partly explain the problems associated with animal models used to study human brain pathologies and could lead to more accurate and effective therapies for human patients.

"First of all, what strikes us most is the time scale that determines the generation and maturation of the neural network. The cultures derived from human cells show a rich and gradual dynamic behaviour, so that the maturation process of the neuronal network generated is clearly observed from 20 days to 45 days of culture", says senior author Daniel Tornero. "During this period, and thanks to the different descriptors that we have developed, we have been able to analyse how the neural network gains in complexity over time, as the human neurons become more and more connected to each other", the researcher adds.

Overall, the findings of this study demonstrate the potential of cellular reprogramming technology to overcome the limitations of animal models and improve the research and treatment of neuropathies.

"These new approaches can be very valuable to validate different therapies preclinically, especially when studying pathologies that affect complex processes based on the organisation of neuronal circuits (neurodevelopmental diseases, autism spectrum disorder, neurodegenerative pathologies, etc.)," explains Tornero.

"In addition, cell reprogramming based on the induction of human pluripotent stem cells would make it possible to generate patient-specific models and, using gene editing tools (such as the CRISPR/Cas9 technique), it would be possible to obtain control cells in which the mutation that causes the pathology is corrected," Tonero concludes.