FORIPS

BAVARIAN RESEARCH NETWORK INDUCED PLURIPOTENT STEM CELLS

Programming and reprogramming of striatal interneurons from human pluripotent stem cells and pericytes

Field of work:

Cell-based therapies represent a promising approach for the treatment of the idiopathic Parkinson´s disease. Whereas the replacement of degenerated nigral dopaminergic neurons is being intensively scrutinized, only few studies so far have focused on the possibility to restore the disease-underlying imbalance of basal ganglia network activity by adding new local interneurons.

In this project we aim at generating human striatal interneurons that can serve for cell-based therapies. To this end, two strategies will be pursued: human induced pluripotent stem cells (iPSC) will be directly programmed into striatal interneurons via development-inspired transcription factors that direct the production of striatal interneurons during embryogenesis; in parallel, pericytes isolated from the adult human brain will be directly reprogrammed without passing through a pluripotent intermediate stage. This dual approach is owed to the fact that iPSC-derived neurons may serve as a source for transplantable cells, whereas the pericyte-derived neurons may open the possibility for endogenous brain repair.

During this funding period, we will characterize the molecular and functional properties of the suchlike generated striatal interneurons and asses their capacity to integrate into the striatal network.

This project may thus lay the scientific foundation for the future employment of striatal interneurons for the treatment of Parkinson´s disease.

Project partners: