Reacción a "Reactions to study in which 'mini-brains' derived from human cells were implanted into newborn rats"

The study represents a major breakthrough in the field of brain organoids. So far there has been much work that has provided fundamental knowledge and robust methodologies for the generation of such cultures, but a major stumbling block in the field remains the lack of maturity and functionality. This study, led by researcher Sergiu Pasca, one of the pioneers in the development of brain organoids, is of excellent quality and incorporates new methodological approaches to overcome certain limitations in conferring complex features in these culture systems.   

To date, brain organoids have provided fundamental knowledge for understanding the embryonic development of this organ, as well as understanding aspects related to the onset of some pathologies. All these advances were limited by important aspects, such as the lack of connectivity of neuronal circuits in a similar way as in the native organ.   

In order to overcome these limitations, Pasca's group has developed a methodology to transplant mini-brains derived from healthy human cells and cells that capture the genetic basis of a rare congenital disease (Timothy syndrome). Specifically, the mini-brains were transplanted into an area of the neonatal rat brain associated with the sensory pathways - the pathways that carry information from the periphery to the cerebral cortex in order to make the information conscious. In this way, the researchers were able to examine the development of the transplanted human cells, as well as their function in vivo. As a result, the researchers observed that once transplanted, the brain organoids develop cell types that had not previously been obtained in vitro, and that after transplantation the organoids integrate both anatomically and functionally into the rat brain.   

Through this approach, the study has been able to observe that this methodological approach allows links to be established between the activity of human cells and learned animal behaviour, showing that neurons from human brain organoids can modulate the activity of rat neurons to drive behavioural responses.  

In this sense, and with a view to further studies, it is conceivable that the methodology employed in this study could be applied in future work aimed at studying neural circuits that are involved in different human pathologies. In fact, in this study, the authors have been able to identify that, after transplantation, organoid neurons present more complex intrinsic functional and morphological characteristics, which has made it possible to identify defects related to Timothy syndrome.  

While the study has important implications in terms of developing strategies to overcome the current limitations in maturing and conferring physiologically relevant characteristics in these cell cultures, the study also shows that the methodological approach used has important limitations, as the differences between the human and rat nervous systems may lead to misinterpretations (as the researchers note in the conclusions of their study).