The DDS research which utilized functional polymers, etc. is created in order to give more new value added in conventional “medicine”, and is developing, This field is developing to “medicine” as intellectualization particle including emulsion, liposome and microsphere which imitated the cell. The way of this DDS research to the intellectualization has presented the way to ultimate place “cell as a medicine” (cytomeclicine). The most intelligent particle which exists on the earth is a cell. The disease therapy using the potential of the cell functions should be established, and the energetic research is carried out. Through generation and differentiation and proliferation of the cell, the disease treatment strategy by the cell in which regeneration amd reconstruction of tissue or organ and organization with the function are enabled. By applying the regeneration science, the treatment strategy using the cell has the limitless possibility.

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Mouse embryonic stem (ES) cell lines have been established from the inner cell mass cells of the blastocysts. ES cells can be maintained in vitro in the undifferentiated state for practically indefinite periods. ES cells can differentiate into various types of cells in vitro and in vivo. Thus, they have been used as good models for cell differentiation during the embryogenesis. Recently, ES cell lines were established from a few species of the primates including the human. Primate ES cells have potency to differentiate into multiple types of somatic cells. This indicates a possibility to use human ES cells as a source for tissue transplantation, and they are expected to solve the current problems of the transplantation therapy such as shortage of the donors. Non-human primate ES cells are valuable in pre-clinical research of the transplantation therapy. We describe an overview of the human ES cells including historical backgrounds of the mouse ES cells. Ethical issues involved in the establishment and clinical use of human ES cells are also discussed.

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For a long time, it had been believed that repairing the nervous system was impassible because the mature nerve cells lacked the ability to regenerate. Recently, it was showed that neural stem cells exist not only in the developing mammalian nervous system but also in the adult nervous system of all mammalian organisms, including humans. Neural stem cells have self-renewal capacity and can differentiate into three major component cells of the brain, neurons, astrocytes and oligodendrocytes. Recently, it was also showed that neurons could be efficiently induced from embryonic stem cells, which can differentiate into every cell type and maintain their undifferentiated status in the presence of LIF. Therefore, neural stem cells and embryonic stem cells are regarded as potential sources for cell transplantation. On the other hand, encapsulated dopamine-secreting cells are also potential donors for a treatment of Parkinson's disease, because encapsulated cells can avoid immunological problems, Nowadays, there is great interest in the possibility of repairing the nervous system by transplanting new cells that can replace those lost through damage or disease, such as Parkinson's disease. In this paper, we are going to review some recent remarkable progress about the regeneration of the nervous system by cell transplantation.

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Blood-brain (BBB) and inner blood-retinal barriers (iBRB) are formed by tight-junction of the brain and retinal capillary endothelial cells, respectively. These barriers are known to restrict the entry of substances from circulating blood to the brain and retina. For the development of new drug targeting system and tissue regeneration of these barrier organs, it would be very important subject to reconstitute barrier organs using in vitro immortalized cell line. Conditionally immortalized brain and retinal capillary endothelial cell lines were established from a transgenic rat (Tg rat) and rnouse (Tg mouse) harboring temperature-sensitive a simian virus 40 (ts SV 40) large T-antigen. These cell lines have temperature-sensitive cell growth due to the expression of is SV 40 large T-antigen and endothelialmarkers. These cell lines have expression of in vivo influx and efflux transporters such as P-glycoprotein, GLUT 1 and MCT 1, demonstrating that these in vitro models would reflect the in vivo conditions. Gene expression of GLUT 1 and enzyme activities of γ-glutamyl transpeptidase and alkaline phosphatase were significantly induced by the co-culture between rat conditionally immortalized brain endothelial cell line (TR-BBB) and conditionally immortalized astrocyte cell line (TR-AST). Our in vitro model system could be very useful tool to clarify the barrier functions, including transporter genes and tight junction proteins and their regulation system.

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Strict regulation of the distribution and degradation kinetics is the ultimate aim of drug delivery system. Regulation of drug delivery would increase the therapeutic efficacy and decrease the potential side effects. We encapsulated and used Z-Asp, a caspase inhibitor in poly-N-p-vinylbenzyl-D-lactonamide (PVLA) coated-poly(L-lactic acid) (PLA)-nanospheres in a mouse model of acute hepatitis. These nanospheres were internalized and accumulated in hepatocytes both in vitro and in vivo. Encapsulation significantly extended the intracellular retention time of the content in hepatocytes, which increased the bioavailability of the caspase inhibitor. In addition, the therapeutic effect was temporally controllable in vivo by modifying the component of the nanospheres. A cocktail of nanospheres with diverse degradation kinetics showed persistent therapeutic effects in acute hepatitis and only nanospheres that targeted hepatocytes and controlled degradation rescued mice from lethel hepatic injury. This temporally and spatially controlled drug delivery system could be used in various liver diseases.

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