Local Hypoxia System As a Sensing Interface of Cellular Responses

摘要

Oxygen concentration is one of the critical factors tightly controlled in each part of an organism to regulate the cells' role and function. Yet, changes in tissue oxygenation often occur in small focal areas with aging or as a result of an injury. Despite the serious health implications of focal hypoxia, no methodologies exist that can model oxygen supply system accordingly in animal models or in vitro models. Therefore, we designed a novel local hypoxia system as a sensing interface for in vitro cell culture. The oxygen removal efficiencies measured by Clark electrodes showed that O_2 concentration can be reduced from 20.9%/140mmHg or 5%/35mmHg and maintained at hypoxia (< 1.5%/10mmHg) in 15 or 8 minutes respectively. The induced hypoxia stimulated localized time-dependent HIF-1α transcription factor nuclear accumulation at the region of interest on human neural progenitor cells. This is the first system capable of robustly generating normoxia and hypoxia side-by-side on the same culture dish for comparative study. The new culture system provides the opportunity to decipher the pathophysiology of hypoxia-related diseases including stroke, dementia and cardiovascular complications.