Innervated adrenomedullary microphysiological system to model nicotine and opioid exposure

Area of Science:

• Physiology
• Neuroscience
• Developmental Biology

Background:

• Transition to extrauterine life requires a catecholamine surge for cardiovascular, respiratory, and metabolic adaptation.
• Mechanisms of adrenomedullary catecholamine release are not fully understood.
• Cesarean delivery and prenatal exposure to nicotine or opioids impair adrenomedullary catecholamine release.

Purpose of the Study:

• To investigate the mechanisms regulating adrenomedullary innervation.
• To develop and utilize a novel bioengineered model for studying the adrenal medulla.

Main Methods:

• Development of compartmentalized 3D microphysiological systems (MPS) using GelPins.
• Utilizing discrete cultures of adrenal chromaffin cells and preganglionic sympathetic neurons within a contiguous microtissue.
• Assessing catecholamine release under varying oxygen conditions and in the presence of opioids and nicotine.

Main Results:

• Adrenal chromaffin innervation is critical for hypoxia-mediated catecholamine release.
• Opioids and nicotine impact adrenal chromaffin cell responses to hypoxia.
• Neurogenic control mechanisms governing catecholamine release remain intact despite opioid and nicotine exposure.

Conclusions:

• GelPin-based MPS provide an effective platform for studying innervated organ systems.
• This model advances understanding of catecholamine release regulation.
• The platform offers potential for improved drug screening in neuroendocrine research.