NeuroBeta: Creating an organ-on-a-chip screening platform of functionally innervated Islets of Langerhans

Samenvatting

The peripheral nervous system (PNS) is known to influence the function of the endocrine pancreas, with indications that neural dysfunction is involved in the onset of Type 1 Diabetes and Type 2 Diabetes. Islets of Langerhans are mini-organs within the pancreas that regulate blood glucose by releasing insulin and glucagon. Nerves are known to directly connect to these islets, however current research tools are insufficient to decipher the role of the PNS on islet function or pathology. The gain of this knowledge can improve therapies and permit earlier intervention in the progression of these debilitating diseases.

To address this knowledge deficit, I will create the first engineered co-culture system of nerves and islets that recapitulates the functional connectivity between the PNS and pancreatic tissue. Combining my knowledge of molecular and neurobiology, the biofabrication resources of Maastricht University (UM), and the support of experts in islet biology, I will realize a 3D in vitro platform that approximates the neuro/islet interface. This will also implement the first optogenetic islet stimulation. This overcomes the lack of control that currently hinders animal studies, where pancreatic responses are obscured by nonselective neural stimulation. Using my knowledge of microscopy and image analysis, I will apply high content screening to investigate islet response to specific neural stimuli. In addition, I will investigate the application of molecules that modulate neural activity to improve islet function.

This platform has broader applications to investigate the emerging role of innervation in other pathologies, such as heart disease, kidney disease, and inflammatory bowel diseases (IBD). This includes research into the role of neural dysfunction, treatment and pharmaceutical discovery, and the development of reinnervation strategies to improve the function of transplanted tissues and organs. This also provides the basis for my future scientific investigations, exploring and exploiting innervation for tissue engineering applications.

Kenmerken

Projectnummer

15900

Hoofdaanvrager

Dr. ir. P.A. Wieringa

Verbonden aan

Maastricht University, UMC+, MERLN Institute for Technology-Inspired Regenerative Medicine

Looptijd

01/09/2017 tot 31/08/2020