Development of a disposable multi-compartment micro-cell culture device

摘要

Our final goal is development of a multi-compartment micro-cell culture system "on-chip animal/human". Towards the final goal, we designed and developed a disposable-type three-compartment micro-cell culture using polydimethylsiloxane (PDMS)-based microfabrication and small magnetic stirrer-based internal pumping system (for disposability and space-saving). The developed device was able to be operated in two different perfusion modes, that is, an each compartment perfusion mode and an entire device perfusion mode, so that cells derived from different tissue/organ can be grown or maintained in different culture protocols and finally they are connected for toxicokinetic studies over the entire device. To evaluate the chemical distribution and biological metabolic processes, we incorporated fat and liver-tissue derived cells in the device because they control the distribution and biotransformation of hydrophobic and carcinogenic chemicals. Liver-derived cells, human hepatocarcinoma Hep G2, were inoculated and cultured in the liver compartment in addition to the fat tissue compartment where mature rat adipocytes were immobilized in a 3D scaffold. Both cells remained attached to the surface in monolayers on the bottom surfaces of each compartment without detachment or forming floating aggregates during perfusion. Rat primary hepatocytes were also stably cultured in the liver tissue compartment. We are now trying fluorescent-based visualization of toxicokinetic processes in the liver compartment in the present and absence of rat tissue compartment in the devices administered with fluorescent and carcinogenic chemicals.