Stretchable mesh-electrodes interfacing human iPSC brain organoids

Projektbeschreibung

Neuronale Vorläuferzellen „wachsen“ auf innovativen weichen Elektroden und zeigen Entwicklungsprozesse im Gehirn

Das Gehirn besteht aus etwa 100 Milliarden Neuronen und fast ebenso vielen Gliazellen. Diese Zellen organisieren sich während der Entwicklung zu strukturell und funktionell unterschiedlichen Gewebearten, die zusammenarbeiten und so die Grundlage u. a. für Kognition, Bewegung, Sinneswahrnehmung und Gefühle schaffen. Inzwischen ist es möglich geworden, nicht nur einzelne Zellkulturen zu züchten, sondern funktionale 3D-Strukturen, die als Organsysteme (Assembloiden) zusammenarbeiten. Allerdings muss die Wissenschaft nun entsprechende Methoden zur Analyse und Manipulation solcher Assembloiden nachliefern. Das Projekt STRELECOID wird innovative dehnbare Netzelektroden in Neurosphären integrieren (Freiform-Cluster neuronaler Vorläuferzellen). Die Elektroden sollen physiologische sensorische Eingaben an das sich entwickelnde „Gehirn“ oder den Assembloiden senden und auch Veränderungen überwachen. Damit sollen Einblicke in häufige schwere neuropsychiatrische Erkrankungen wie Schizophrenie und Autismus gewonnen werden.

Ziel

Recent advances in cellular engineering allow to recruit skin cells from donors and reprogram them into neural stem cells. These induced pluripotent stem cells (iPSC) bear the genetic code of the human patient. Efforts to culture these cells in-vitro have been successful in creating a wide variety of 3D arrangements called neurospheres. Because the human central nervous system is by and large inaccessible at all developmental stages, these functional tissue preparations are invaluable. Furthermore, clinical studies performed in animal models are known to translate poorly to humans and therefore these systems provide unprecedented advantages: human neurons in a controlled environment that have the genetic signature of psychiatric or mental disorders borne by the donor patient, such as Alzheimer’s or Parkinson’s disease. Finally, compared to animal studies where overwhelmingly only male animals are studied, stem cell research can operate on both sexes.
The combination of new biomaterials, genome engineering and massively parallel single-cell transcriptomics opens opportunities to precisely study human brain disease
A new exciting development is the possibility to form so-called assembloids, whereby organoids of different brain regions, as for example cortical and thalamic neural ensembles, are brought in proximity and self-assemble into anatomically correct brain regions. These approaches are necessary to study disorders like epilepsy. However these cultures lack physiological sensory input which are key in the development of mental plasticity. Here we plan to overcome this limitation by integrating new mesh-based electrodes that integrate seamlessly into brain tissue and expand symbiotically with the neurosphere as it grows, and thereby have a spatially refined mean to measure but also elicit neural activity. This will shed light on how electric maturation of these neurospheres comes about and help shape them to an anatomically more faithful brain model.