Although it was long thought that the damaged adult central nervous system (CNS) cannot regenerate, spinal cord injury (SCI) is now an important target in regenerative medicine. A series of studies on stem cell-based therapies for SCI has led us to believe that neural stem/progenitor cells (NSPCs) are a promising source for neural tissue replacement therapy after SCI, when applied appropriately. In this review, we summarize our previous findings on stem cell therapies for SCI and discuss the future directions of this work.

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Prostaglandin(PG) D₂ and PGE₂ are major cyclooxygenase metabolites of arachidonic acid produced during allergic reactions including asthma. However, the role of PGD₂ and PGE₂ in allergic inflammation has long been ambiguous. This is partly because non-steroidal anti-inflammatory drugs that inhibit prostanoid synthesis are generally ineffective in allergic disorders. Both PGs exert their actions by acting on G-proteincoupled receptors; PGD₂ acts at the PGD receptor(DP), PGE₂ acts at four subtypes of PGE receptor, EP1 to EP4. To dissect the roles of PGD₂-DP pathway and each PGE₂-EP pathway in allergic reactions, we subject mice deficient in DP, EP1, EP2, EP3 and EP4 receptor individually to ovalbumin-induced allergic asthma as a model of type I allergy. These studies have revealed that there are opposing actions between two prostanoid pathways in allergic reactions; PGD₂-DP pathway and PGE₂-EP3 pathway. We found that the PGD₂ is an important mediator of allergic responses and that PGE₂-EP3 signaling negatively regulates progression of allergic inflammation. This review focuses on the opposite roles of these prostanoid pathways in allergic reactions obtained by our studies and other studies. These findings suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of allergic diseases, such as bronchial asthma, allergic rhinitis and conjunctivitis.

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In artificial internal organs, smaller is better. And an important issue is bio affinity. From these points of view, Regenerative medicine and Nano technology are very useful technology. In Tohoku University, various artificial internal organ research including Artificial esophagus, Artificial Myocardium, and Artificial sphincter based on 21 COE program. Ideal artificial organs may be embodied in future.

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Although the role of interleukin(IL)-6 in inflammatory disease has been previously examined, its role in hemostasis, fibrinolysis, and coagulation during inflammation remins to be established. The present study reviewed the role of IL-6 in hemostatic and coagulatory changes during inflammation, with special emphasis on the inflammation induced by intraperitoneal administration of lipopolysaccharide in IL-6 null^-/- mice and corresponding wild type(WT) mice. After LPS challenge, IL-6^-/- mice revealed significant prolongation of prothrombin time and partial thromboplastin time and a significant decrease in platelet counts as compared with WT mice. LPS treatment induced marked pulmonary hemorrahage with neutrophilic inflammation in IL-6^-/- mice, in contrast, only mild neutrophilic infiltration in WT mice confirmed by macroscopic and histological findings. The protein levels of proinflammatory mediators in the lungs were significantly greater in IL-6^-/- mice than in WT mice after LPS challenge. Our results conclude that IL-6 is protective against coagulatory and hemostatic disturbance and subsequent pulmonary hemorrhage induced by bacterial endotoxin, at least party, via the modulation of proinflammatory processes. In addition, our studies suggest that anti-IL-6 therapy may not be efficient for systemic inflammatory disease such as disseminated intravascular coagulation, acute lung injury, and sepsis.

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Human umbilical cord blood (UCB) cells have many advantages as a source of cell transplantation because of their immaturity compared with adult cells. Here, with a view to utilize UCB for cell transplantation into injured liver, we investigated whether UCB cells have a potential for differentiation into functional hepatocyte-like cells (HLCs).
UCB cells were cultured in the primary culture system supplemented with a combination of FGF-1, FGF-2, LIF, SCF and HGF. About 50% of the adherent UCB cells expressed albumin (ALB) and hepatocyte-lineage markers were co-expressed in the ALB-positive cells. Then, in the model for cell transplantation into NOD/SCID mice with transient liver injury, human UCB-derived HLCs were detected in the recipient-livers. And, the UCB-derived HLCs secreted human ALB into the recipient-sera. Moreover, in the model for cell transplantation into SCID mice with chronic liver damage, the engrafted UCB cells appeared at higher frequencies than the model with transient damage, and human ALB was abundantly expressed in UCB-derived HLCs in the recipient-liver.
This study provides the evidence that UCB can supply functional HLCs. UCB could be a potential source of cell transplantation for liver injury.

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INTRODUCTION: Mesalazine(Pentasa) is widely used for ulcerative colitis(UC). However, the anti-inflammatory actions of Mesalazine are not fully understood. In this study, we evaluated the actions of Mesalazine in vitro on the functions of neutrophil, a major inflammatory cell. Furthermore, we evaluated the combined effects of Mesalazine and sodium ferrous citrate(SFC) on neutrophil functions, since SFC is clinically administered to UC patients together with Mesalazine for treatment of chronic anemia associated with UC.
METHODS: Superoxide production by neutrophils was measured on the basis of superoxide dismutaseinhibitable cytochrome c reduction. Preincubated neutrophils were stimulated with fMLP, PMA or complement-opsonized zymosan particles. Cytochrome c reduction was calculated by the absorbance difference at 550 nm. Neutrophil migration was measured by a Boyden chamber assay with using zymosan-activated serum (C5a) as a chemotactic factor. Neutrophils were preincubated in the presence of 0.01-0.5mM Mesalazine and then incubated with fMLP. The cells were further incubated with phycoerythrin (PE)-labeled anti-CD11b monoclonal antibody, and the expression of CD11b was analyzed by flow cytometry. Neutrophils were preincubated with 5μg/ml SFC and 0.01-0.1mM Mesalazine, and superoxide generation and migration were measured.
RESULTS: Mesalazine dose-dependently inhibited the superoxide production induced by PMA and fMLP at > 0.05 mM. Furthermore, Mesalazine inhibited chemotaxis toward zymosan-activated serum in a dosedependent fashion. Moreover, 0.5mM Mesalazine inhibited the fMLP-induced up-regulation of CD11b expression. Interestingly, Mesalazine combined with SFC inhibited the superoxide generation and migration by neutrophils, compared with Mesalazine alone. Thus, the present observations suggest that a combined administration of Mesalazine and SFC may have a potential to reduce mucosal injury by suppressing neutrophil functions (migration, ROS generation and expression of adhesion molecule) in UC.

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BACKGROUND AND PURPOSE: The inflammatory bowel diseases(IBD) such as ulcerative colitis(UC) are intractable diseases of unknown origin. The mucosal injury of UC is presumed to be partly caused by reactive oxygen species(ROS) produced by neutrophils. Chronic inflammation of UC results in chronic anemia, to which iron is given. In this study, to evaluate the effect of sodium ferrous citrate(SFC) on neutrophil functions, we measured superoxide generation and migration of neutrophils treated with SFC in vitro.
METHODS: Superoxide generation induced by phorbol myristate acetate(PMA), opsonized zymosan(OPZ) and N-formyl-menthionyl-leucyl-phenylalanine(fMLP) was determined based on the superoxide dismutaseinhibitable cytochrome c reduction. To further clarify the inhibitory mechanism of SFC, the membrane fraction was isolated and NADPH-dependent superoxide production was measured. Moreover, neutrophil migration was evaluated with a Boyden chamber assay using zymosan-activated serum (C5a) as a chemoattractant.
RESULTS: SFC dose-dependently inhibited the superoxide production induced by all the stimuli examined. Similarly, SFC-treatment inhibited the activity of NADPH oxidase in the membrane fraction of neutrophils. In addition, SFC suppressed chemotaxis toward zymosan-activated serum in a dose-dependent fashion.
CONCLUSIONS: In this study, we revealed that SFC could suppress neutrophil functions such as superoxide generation (NADPH oxidase activity) and migration. During episodes of IBD, stimulated neutrophils are accumulated in inflamed mucosa via the migration through vascular endothelium, where they release ROS such as superoxide. Thus, the present observations suggest that SFC may have a potential to reduce mucosal injury by suppressing migration and ROS generation by neutrophils in UC.

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