(IMCS First Place Best Paper Award) Local Hypoxia System as a Sensing Interface of Cellular Responses

Abstract

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 O2 concentration can be reduced from 20.9% / 140mmHg or 5% / 35mmHg and maintained at hypoxia (< 1.5% / 10mmHg) in 15 or 8 minutes respectively, compared with 3 hours needed by conventional incubator and hypoxic chambers. The induced hypoxia stimulated localized time-dependent HIF-1α transcription factor nuclear accumulation at the region of interest on human neural progenitor cells. This new culture system can robustly generate a hypoxia gradient in the same culture dish for the first time and provides the opportunity to decipher the impact of focal hypoxia, the function of localised oxygen homeostasis and the pathophysiology of multiple diseases.