Abstract
The transition to extrauterine life results in a critical surge of catecholamines necessary for increased cardiovascular, respiratory, and metabolic activity. The mechanisms mediating adrenomedullary catecholamine release are poorly understood, given the sympathetic adrenomedullary control systems’ functional immaturity. Important mechanistic insight is provided by newborns delivered by cesarean section or subjected to prenatal nicotine or opioid exposure, demonstrating the impaired release of adrenomedullary catecholamines. To investigate mechanisms regulating adrenomedullary innervation, we developed compartmentalized 3D microphysiological systems (MPS) by exploiting the meniscus pinning effect via GelPins, capillary pressure barriers between cell-laden hydrogels. The MPS comprises discrete 3D cultures of adrenal chromaffin cells and preganglionic sympathetic neurons within a contiguous bioengineered microtissue. Using this model, we demonstrate that adrenal chromaffin innervation plays a critical role in hypoxia-medicated catecholamine release. Furthermore, opioids and nicotine were shown to affect adrenal chromaffin cell response to a reduced oxygen environment, but neurogenic control mechanisms remained intact. GelPin containing MPS represent an inexpensive and highly adaptable approach to study innervated organ systems and improve drug screening platforms by providing innervated microenvironments.
Publisher
Cold Spring Harbor Laboratory
Reference63 articles.
1. Peripheral and central effects of circulating catecholamines;Compr Physiol,2015
2. Adrenomedullary response to maximal stress in humans
3. K. L. Olson , D. T. Marc , L. A. Grude , C. J. McManus , G. H. Kellermann , The Hypothalamic-Pituitary-Adrenal Axis: The Actions of the Central Nervous System and Potential Biomarkers. American Academy of Anti-Aging Medicine XIII.
4. Fetal Physiology and the Transition to Extrauterine Life