Microchimeric fetal cells are present in the maternal body over a long period and thought to have the ability to colonize multiple tissues and organs. They are found in a wide range of maternal tissues affected with variety of diseases, thus, there is a possibility that they may contribute tissue repair and regeneration. To assess their possibility of use in regenerative medicine, we investigated whether fetal cells regenerate infracted maternal organs.
  We crossbred wild female mice with male transgenic mice, expressing enhanced green fluorescent protein (EGFP), and total hysterectomies were performed at the day 6 of pregnancies. On day 60 after the operations, the mice were injected with streptozotocin (STZ) to induce multiple organs injuries. We also created the ischemic organ injury model ; myocardial infarction model and cerebral infarction model. Detection and quantification of fetal cells were then attempted in a variety of maternal organs via a fluorescent microscope and quantitative PCR amplification of the gfp transgene. Fetal cells were detected only in maternal bone marrow before maternal organs injuries were induced, however, they were detected not only in bone marrow but also in the maternal injured organs. Histological analysis showed that differentiated fetal cells were observed and their morphological appearance was indistinguishable from their maternal counterparts.
  These results indicate that fetal cells sustained their population in the maternal bone marrow, may have contributed to the maternal tissue regeneration.

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  Microchimerism is defined by the presence of circulating cells, bi-directionally transferred from one genetically distinct individual to another. The acquisition and persistence of fetal cell microchimerism, small numbers of genetically disparate cells from the fetus in the mother, is now a well-recognized consequence of normal pregnancy. Some of the autoimmune diseases that show a predilection for women in their child-bearing years and beyond are linked to fetal microchimerism from previous pregnancies. Microchimerism has been investigated in different autoimmune disorders, such as systemic sclerosis, systemic lupus erythematosus, autoimmune thyroid diseases, and primary biliary cirrhosis. Recent data have demonstrated the promising role of microchimeric cells in the maternal response to tissue injuries by differentiating into many lineages. Therefore, further understanding of fetal-maternal microchimerism may help in anticipating its implications in disease as well as in more general women's health issues.

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  To translate research findings into medicine and drug development, we have been performing in vivo research using primary human samples. Development of mouse models with reconstituted human immunity would be critical to overcome technical and ethical constraints associated with in vivo human research. To this end, we have created humanized mice by intravenously injecting purified human hematopoietic stem cells (HSCs) into immune-compromised NOD/SCID/IL2rgKO newborns. This xenogeneic transplantation system allows long-term engraftment and multi-lineage differentiation of human HSCs. The humanized mouse fully reconstituted with human myeloid and lymphoid subsets is expected to serve as an in vivo platform for the investigation of human immune function.
  In addition to understanding normal human hematopoiesis and immunity, the use of humanized mice is expected to allow investigators to translate their research findings into therapeutic and pharmaceutical development. As a possibility for such translation, we developed an in vivo model of human acute myeloid leukemia (AML), a disease in which the majority of patients succumb to relapse. Using the model, we examined the pathogenesis of AML and tried to clarify the role of AML stem cells in chemotherapy resistance and relapse. Humanized mouse model for both normal and diseased immuno-hematopoietic system is opening a new era in translational medicine.

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  Primary immunodeficiency diseases (PID) represents a group of inherited diseases where mutations in certain gene lead to certain levels of defects in patient immune systems. Among them, several types of PID, including severe combined immunodeficiecny (SCID), warrented development of new types of curative treatment other than allogeneic hematopoietic stem cell transplantation, eventually culiminating in successful stem cell gene therapy tials such as the cases for adenosine deaminase (ADA)-deficiency SCID patients. In this article, I will summarize the current status of stem cell gene therapy for PID, and discuss the problems such clinical trials have in the present forms of treatment, e.g., possible risks of leukemogenesis due to insertional mutagenesis by the use of therapeutic viral vectors. I also try to discuss the future of this type of experimental medicine aiming for the permanent cure of PID, including the one utilizing innovative technologies such as induced pluripotent stem cells.

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  Takayasu's arteritis (TA) is a chronic idiopathic inflammatory disease affecting primarily aorta and its proximal branches. Pediatric patients with TA tend to have more severe clinical course and be refractory to conventional treatments compared with adults. Corticosteroids are major treatment of TA, however, high dose is required to get remission. Particularly, adolescent patients are usually suffering from side-effects of excessive dose of corticosteroids. Immunosuppressants are added expecting the corticosteroid sparing agents. However, some patients, such as HLA-B52 positive, tend to be registant to these conventional treatments. Recently, several reports showed the efficacy of Infliximab, anti-tumor necrosis factor (TNF) alpha monoclonal antibody, for adult patients with refractory TA. We described three cases of adolescents with TA treated with Infliximab. It was initially effective in all three patients. However, serious infusion reaction occurred in one of them during 11^th times of Infliximab infusion and she discontinued the therapy. Other two patients showed good response in initial phase, but clinical manifestations and laboratory findings became worse after several months. In these patients with secondary failure to Infliximab, increased dosage and shortening the interval of infusions provided effectiveness again.
  Infliximab would be a good choice for adolescent patients with TA refractory to conventional treatments. However, we should carefully monitor safety and efficacy of this agent considering its peculiarity.

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  A 61-year-old woman with a continuous left temporal headache and a fever of 39°C for about one month was admitted to our hospital. The physical examination was not remarkable, except for slight tenderness of the left temporal side of her head. Laboratory data on admission revealed an increase of leucocytes (9,700/μl), blood platelets (59.4×10⁴/μl), and serum c-reactive protein (CRP) (10.9 mg/dl). The erythrocyte sedimentation rate (ESR) was also elevated (88 mm/1 h). After gallium scintigraphy, a gallium-67 uptake was weakly detected at the left temporal side of her head. However, after FDG-PET examination, a high FDG uptake was detected in her temporal artery, abdominal aorta, and bilateral femoral arteries. Moreover, Doppler sonography showed a hypoechoic halo around her left temporal artery. After treatment with oral prednisolone (40 mg/day), her headache disappeared and her serum CRP level returned to normal. Finally, the patient had pathological temporal arteritis proven by a biopsy.
  It is difficult to make an early diagnosis of temporal arteritis if the dilatation or swelling of the temporal arteries is not present. FDG-PET is considered a useful examination not only for the exploration of tumors, but also for the evaluation of the inflammation of large vessels.

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  The present case is the first report of a systemic lupus erythematosus patient which has been induced Parkinsonism with the administration of tacrolimus (TAC). A 50-year-old woman was diagnosed as lupus nephritis on September 2003. The patient had been prescribed initially 40 mg/day of prednisolone, then cyclosporine was added on May 2005. One year later, she developed severe headache, so cyclosporine was stopped, and she was prescribed tacrolimus on February 2007. However her severe headache had been disappeared, she experienced rigidity and tremor around September 2007. The Dopamine-transporter-imaging examination reavealed that she had Parkinson's disease. The gene analysis on the genetic background showed her case was the sporadic type? Parkinson's disease. Washing out of Tacrolimus, her Parkinsonism was partially improved. This fact suggested that her Parkinsonism was drug-induced type Parkinsonism. In lupus nephritis patients who have been treated with TAC, a very careful observation should be considered because neurological disorders inducing Parkinsonism may occur.

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