Dr. Katrin Schrenk-Siemens
Institute of Pharmacology, Medical Faculty Heidelberg, Heidelberg University
Dr. Claudio Acuna Goycolea
Institute of Anatomy and Cell Biology, Medical Faculty Heidelberg, Heidelberg University
Human pluripotent stem cell-derived neurons as a tool to study central and peripheral nociceptive mechanisms
A translational human cell-based platform to study nociception mechanisms and to test for efficacy, toxicity, and tolerance of novel pain drugs in vitro.
Background and central theme
Recent advances in stem cell biology have facilitated the study of human brain disorder mechanisms as well as screening for novel drugs to treat human diseases using actual human neurons. In this project, we propose to develop a translational platform to produce multiple types of functional cells derived from human pluripotent stem cells (hPSCs). These cells will be used in the context of pain research to address three key issues. First. For early stage validation of results derived from rodent studies, now in neurons of human origin. Second. For establishing a novel co-culture system combining different cell-types (neuronal and non-neuronal cells) involved in pain-related mechanisms. Third. Utilizing the co-culture system to investigate basic properties in pain-relevant human pathways with the possibility of early stage screening or testing of novel pain drugs.
Approach and main goals:
Our project aims to capitalize on novel approaches to differentiate hPSCs into different classes of human neuronal and non-neuronal cells relevant for pain research, and further on to reconstruct in vitrosimple neuronal and non-neuronal interactions commonly found in the nervous system using a custom compartmentalized culture system that facilitates the formation of functional interaction between different types of differentiated cells. We propose four distinct but complementary aims:
Translational goals and collaborations of SO2 project.
- To establish a pipeline to produce different types of peripheral and central human neuronal and non-neuronal cells relevant for pain research with high-efficiency.
- To establish a compartmentalized culture system based on microfluidic devices to simultaneously differentiate different cell types that form functional interactions between them.
- To analyze in detail the basic properties of pain-relevant human neural pathways consisting of peripheral and central neurons using morphological, functional and genomic approaches.
- To develop strategies to differentiate non-neuronal cells of great relevance for pain research and to reconstruct interactions between human neuronal and these non-neuronal partners.