PhD defence P.A. (Pien) Goldsteen

A human in vitro model for airway neuro-effector interactions

The research of Pien Goldsteen shows that it is possible to make a human model to enable communication between the nervous system and the lungs on a chip.

Goldsteen: "Airway nerves play a key role both in the development of the bronchial hyper-responsiveness and in chronic cough associated with asthma. However, there is an inherent difficulty in studying complex cell-cell interactions that characterize neuro-effector responses in asthma using laboratory animals. Due to recent technological advances, it is now possible to develop a human in vitro model by combining human pluripotent stem cell (hPSC) and organ-on-a-chip technology. The results of this thesis show that we are able to develop a protocol in which we differentiated hPS cells into cholinergic airway nerves. First, the hPS cells were differentiated to a vagal neural crest precursor, and then to cholinergic airway nerves using the neurotrophin BDNF. About 30% of the hPS cells were converted into these airway nerve cells, which is quite efficient. This was confirmed by expression of β-3-tubulin and ChAT, special markers for cholinergic neurons. Furthermore, neurons responded to acetylcholine and potassium chloride (KCl), demonstrating that they are also functional.Subsequently, a PDMS microfluidic chip was fabricated to further study nervous system function. Airway smooth muscle cells play an important role in bronchial hyperresponsiveness. Neurons and smooth muscle cells were cultured in the individual compartments in the chip, which were connected via microchannels to allow axonal communication, as happens in the body. When cholinergic neurons and smooth muscle cells were cultured in the chip, the axons innervated the smooth muscle cells in the other compartment, enabling the study of neuronal communication."

Promotores Prof.dr. R. Gosens and Prof.dr. A.M. Dolga