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A Micro-fluidic Approach using
                                                                                                  a Super-functional Liver Chip
                                                                                                        Micro-fluidic
               Data


               Using embryonic stem cells and iPS (mouse and human),   shown in Fig. 2. We have been developing an in vitro flow
               liver tissue-like structures were successfully modeled as   system, including hepatic tissue construction with this new
                           (1)
               shown in Fig. 1 . In addition, hepatocytes could migrate   co-culture technology, which is different from a single
                                                        (2)
               to the endothelial cell network formed on an EHS gel  as   culture chip model using hepatocytes only.   iPS Cell Differentiation  Proteomic Analysis of Human


















                                                                                        HUVEC Network on EHS gel        of  Human ES Cells  Comparative Metabolomics
                                                                                                   Bar:500 µm
                  Fig. 1  Mouse ES cell-derived hepatic tissue morphology,
                             at 23 days after the induction of  differentiation ,     Primary hepatocytes
                                                       (1)
                             Green : endothelial cells, Red : hepatocytes                                              a Super-functional Liver Chip  A Micro-fluidic Approach using

                  8
                       Cyp2d9, 2b
                16?-hydroxylation activity  4 2                                                                        by LC-MS/MS  Metabolomics
                  6










                  0
                         Non-Flow  Flow     Non-Flow  Flow


                          Hepatocytes          IVLEHS
                                                                                                Bar:200 µm
                         Fig. 3 Testosterone metabolism analysis                                                       by MALDI  Tissue Imaging
                                                                        Fig. 2 In vitro liver sinusoidal model (IVLEHS)  (2)

               Even if primary hepatocytes were cultured, the hepatic   retinal pigment epithelial cells of iPS cell origin (with
               activities in the culture were much higher with flow than   grants from JST) and the chip for evaluating the adhesion
               without flow (Fig. 3). The activities of the IVL chip with   conditions of osteoblast cells, and others. We are
               flow were the highest of all. These results suggest that   contributing to the research field of cell analysis utilizing
               medium flow, as well as hepatic tissue construction, is   micro fabrication, micro fluidic technology, evaluation
               important for liver-specific activities (Fig. 3). Shimadzu is   technology, and other advanced techniques.
               engaged in the development of the chip treating the                                                     Spectrometers  Shimadzu’s Mass

               (1)Ogawa, S., et. al. , Stem Cells, 23 :903-913,2005
               (2)Toyoda, Y., et .al.,  Drug Metab Dispos, 40 :169-177, 2012




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