H Iwata

Kyoto University, Kyoto, Kyoto-fu, Japan

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Publications (366)1088.33 Total impact

  • Ian Torao Hoffecker, Hiroo Iwata
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    ABSTRACT: Co-localization of islets with immuno-privileged cell types such as mesenchymal stromal cells (MSC's) is a potentially multifaceted and adaptive approach to islet protection. We attempted to co-localize MSC's with islets by creating single-celled suspensions of MSC's and cells from dissociated islets on top of arrays of round bottom wells. Segregation between islet-derived cells and MSC's was observed within 3 days. When ROCK inhibitor Y-27632-containing media was used during the preparation of MSC/islet co-aggregates, co-aggregates sorted into core-shell structures with islet-derived cells occupying the exterior while MSC's occupied the core. Immunostaining revealed that MSC-derived regions transition from expression of N-cadherin, vimentin, and CD44 to expression of E-cadherin, while pan-cadherin staining indicated re-allocation of cadherins to cell borders, and shear-based cohesion measurements pointed to increased cohesive strength. The switch suggests that MSC-islet cohesion improved due to the greater degree of cell-cell adhesive compatibility. Functional evaluation of MSC-islet co-aggregates confirmed normal insulin secretory function and partial suppression of anti-CD3-activated splenocyte proliferation. These findings demonstrate that manipulation of cell-cell interactions can be harnessed to control spheroid architecture in MSC-islet co-aggregates, and this study also provides the basis for future islet therapies.
    Tissue Engineering Part A 01/2014; · 4.64 Impact Factor
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    ABSTRACT: Transplantation of islets of Langerhans (islets) was used to treat insulin-dependent diabetes mellitus. However, islet grafts must be maintained by administration of immunosuppressive drugs, which can lead to complications in the long term. An approach that avoids immunosuppressive drug use is desirable. Co-aggregates of Sertoli cells and islet cells from BALB/c mice that were prepared by the hanging drop method were transplanted into C57BL/6 mouse liver through the portal vein as in human clinical islet transplantation. The core part of the aggregates contained mainly Sertoli cells, and these cells were surrounded by islet cells. The co-aggregates retained the functions of both Sertoli and islet cells. When 800 co-aggregates were transplanted into seven C57BL/6 mice via the portal vein, six of seven recipient mice demonstrated quasi-normoglycemia for more than 100 days. The hanging drop method is suitable for preparing aggregates of Sertoli and islet cells for transplantation. Notably, transplantation of these allogeneic co-aggregates into mice with chemically induced diabetes via the portal vein resulted in long-term graft survival without systemic immunosuppression.
    Transplantation 12/2013; · 3.78 Impact Factor
  • Sho Deno, Naohiro Takemoto, Hiroo Iwata
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    ABSTRACT: Ischemia-reperfusion damage is a problem in organ transplantation. Reactive oxygen species are produced in cells by blood-mediated reactions at the time of blood reperfusion. In this study, we developed a method to immobilize and internalize antioxidants in endothelial cells, using vitamin E-loaded liposomes. The liposomes loaded with vitamin E and human umbilical vein endothelial cells (HUVECs) were modified with poly(ethylene glycol)-phospholipid conjugates carrying 20-mer of deoxyadenylic acid (oligo(dA)20) and 20-mer of complementary deoxythymidylic acid (oligo(dT)20), respectively. The liposomes were effectively immobilized on HUVECs through DNA hybridization between oligo(dA)20 and oligo(dT)20. The liposomes loaded with vitamin E were gradually internalized into HUVECs. Then, the cells were treated with antimycin A to induce oxidative stress. We found the amount of reactive oxygen species was greatly reduced in HUVECs carrying vitamin E-loaded liposomes.
    Bioorganic & medicinal chemistry 11/2013; · 2.82 Impact Factor
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    ABSTRACT: Cell behavior can be manipulated by the topography of the culture surface. In this study, we examined the intercellular communication and osteogenic differentiation of mesenchymal stem cells (MSCs) grown on electrospun fibers with different orientations and densities. Human bone marrow-derived MSCs (hMSCs) were seeded on poly(ε-caprolactone) (PCL) electrospun scaffolds composed of aligned (1D) or cross-aligned (2D) fibers (1.0-1.2 µm diameter) with high, medium, or low fiber densities. It was found that cells preferred to adhere onto electrospun PCL fibers rather than on the flat substrate. The immunofluorescence staining showed that the expression of vinculin, a focal adhesion protein, was limited to the periphery and the two extremities of aligned cells on the edge of the fibers. Electron microscopy showed that cells extended their lamellipodia across the adjacent fibers and proliferated along the direction of fibers. Cells grown on 1D fibrous scaffolds at all fiber densities had an obvious alignment. On 2D fibers, a higher degree of cell alignment was observed at the higher fiber density. On 1D scaffolds, the gap junction intercellular communication (GJIC) quantified by the lucifer yellow dye transfer assay was significantly promoted in the aligned cells in the direction parallel to the fibers but was abolished in the direction perpendicular to the fibers. The expression of osteogenic marker genes (RUNX2, ALP, and OCN) was significantly enhanced in seven days by culture on 1D but not 2D fibers. It was thus proposed that the promoted osteogenic differentiation of hMSCs may be associated with the fiber-guided and directional induction of GJIC.
    Biomedical Materials 09/2013; 8(5):055002. · 2.17 Impact Factor
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    ABSTRACT: Poor viability of cells transplanted into the brain has been the critical problem associated with stem cell-based therapy for Parkinson's disease. To overcome this problem, a collagen hydrogel incorporating an integrin-binding protein complex was prepared and used as a carrier for neural stem cells. The protein complex consisted of two polypeptides containing the G3 domain of a laminin alpha-1 chain and the C-terminal oligopeptide of a laminin gamma-1 chain. These polypeptides were fused with alpha-helical segments which spontaneously formed a coiled-coil heterodimer and with the collagen-binding peptide that facilitated the binding of the heterodimer to collagen networks. In this study, neural stem cells stably expressing the enhanced green fluorescent protein (EGFP) were suspended in the hydrogel and transplanted into the striatum of healthy rats. The viability of transplanted cells was evaluated by histological analysis and quantitative reverse-transcriptase polymerase chain reaction for EGFP mRNA present in the tissue explants. Our results showed that the collagen hydrogel incorporating the integrin-binding protein complex serves to improve the viability of NSCs in the early stage after transplantation into the striatum.
    Bioconjugate Chemistry 08/2013; · 4.58 Impact Factor
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    ABSTRACT: Human neural progenitor cells (hNPCs) are a potential source for cell transplantation therapy in central nervous disorders. Neurosphere culture, the standard method for obtaining hNPCs, suffers from several limitations including the heterogeneity of cells in a neurosphere and the limitation of growth rate due to the presence of differentiated cells in the neurospheres. To overcome these limitations, we developed culture substrates that enable the selective expansion of hNPCs in adherent culture. Epidermal growth factor and basic fibroblast growth factor were fused with hexahistidine (EGF-His and bFGF-His, respectively) and were immobilized alone or in combination onto Ni ion-bound glass through coordination. When hNPCs derived from human fetal brain were cultured on these substrates, adhesion and proliferation of hNPCs took place most efficiently on the substrate with both EGF-His and bFGF-His compared to substrates with either factor alone and to a control substrate without growth factors. The rate of cell proliferation was two-fold higher in the adherent culture on the substrate immobilized with both EGF-His and bFGF-His than in the standard neurosphere culture. A cell population obtained after 5 days of culture on the substrate contained nestin-expressing progenitors (>90%). We conclude that the culture substrate with co-immobilized EGF and bFGF is effective for the selective expansion of hNPCs.
    Biomaterials 05/2013; · 7.60 Impact Factor
  • Nguyen Minh Luan, Hiroo Iwata
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    ABSTRACT: Intraportal transplantation of islets of Langerhans is followed by marked islet loss, mainly caused by instant blood-mediated inflammatory responses (IBMIR). We previously developed a method of co-immobilizing sCR1 and heparin on islets. Here we examined whether this process could reduce islet loss following intraportal islet transplantation in a syngeneic mouse model. sCR1-heparin islets or unmodified islet controls were transplanted into the livers of streptozotocin-induced diabetic mice. Transplantation of 100 and 125 sCR1-heparin islets normalized blood glucose levels in 8 of 9 (88.9%) and 9 of 9 diabetic mice (100%), respectively, whereas transplantation of 100 and 125 non-treated islets induced normoglycemia in 0 of 9 and 2 of 9 diabetic mice, respectively. Fibrin staining and plasma insulin measurements indicated that, compared to non-treated islets, sCR1-heparin islet transplantation was associated with fewer blood clots around islets, and significantly less insulin leakage from damaged islets at 1 h post-transplantation. Long-term follow-up of the sCR1-heparin islet group showed islet cells in the livers and insulin expression. In conclusion, co-immobilization of sCR1 and heparin on islets could effectively reduce islet damage by IBMIR, and might be useful to enable transplantation with only one donor and one recipient.
    Biomaterials 04/2013; · 7.60 Impact Factor
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    ABSTRACT: BACKGROUND: Transplantation is one potential clinical application of neural stem cells (NSCs). However, it is very difficult to monitor/control NSCs after transplantation and so provide effective treatment. Electrical measurement using a poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) modified microelectrode array (MEA) is a biocompatible, non-invasive, non-destructive approach to understanding cell conditions. This property makes continuous monitoring available for the evaluation/assessment of the development of cells such as NSCs. METHODS: A PEDOT-PSS modified MEA was used to monitor electrical signals during NSC development in a culture derived from rat embryo striatum in order to understand the NSC differentiation conditions. RESULTS: Electrical data indicated that NSCs with nerve growth factor (NGF) generate a cultured cortical neuron-like burst pattern while a random noise pattern was measured with epidermal growth factor (EGF) at 4 days in vitro (DIV) and a burst pattern was observed in both cases at 11 DIV indicating the successful monitoring of differentiation differences and developmental changes. CONCLUSIONS: The electrical analysis of cell activity using a PEDOT-PSS modified MEA could indicate neural network formation by differentiated neurons. Changes in NSCs differentiation could be monitored. GENERAL SIGNIFICANCE: The method is based on non-invasive continuous measurement and so could prove a useful tool for the primary/preliminary evaluation of a pharmaceutical analysis.
    Biochimica et Biophysica Acta 02/2013; · 4.66 Impact Factor
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    ABSTRACT: Sertoli cells play a crucial role in creating the immunoprivileged environment of the testis. We examined the survival of islets of Langerhans after co-transplantation with Sertoli cells. Sertoli cells near islets should protect the graft from rejection. In this study, conjugates of single stranded oligonucleotides, poly(ethylene glycol) and phospholipids (ssDNA-PEG-DPPE) were used to immobilize Sertoli cells on islets. The 20-mer of deoxyadenylic acid (oligo(dA)20) and 20-mer of deoxythymidylic acid (oligo(dT)20) were presented as ssDNAs on the surfaces of Sertoli cells and islets, respectively, through the hydrophobic interaction between a lipid unit of the conjugates and the cell membrane. The Sertoli cells were immobilized on the islets through hybridization between oligo(dA)20 and oligo(dT)20. When Sertoli cell-immobilized islets were infused into the liver of mice through the portal vein, the Sertoli cells remained around the islets.
    Biomater. Sci. 02/2013; 1(3):315-321.
  • Tomonobu Kodama, Hiroo Iwata
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    ABSTRACT: Endovascular treatment of intracranial aneurysms with detachable coils has been accepted widely. Problems of coil compaction, recanalization and rare endothelialization at the aneurysm orifice are not yet solved. We investigated the efficacy of a simvastatin coating applied without any additional matrix to coils to accelerate thrombus organization in the cavity in a rat model of aneurysm. Twelve metal coils coated with simvastatin and 12 bare coils were inserted into the ligated external carotid arterial (ECA) sacs of rats. The ECA sacs were removed 2 or 4 weeks after the coils were implanted and examined by histology and immunohistochemical assay. The organized areas in the ECA sacs in the simvastatin group (73.6 ± 19.4%, 2 wk; 83.4 ± 11.1%, 4 wk) was significantly higher p = 0.003, 2 wk; p = 0.0004, 4 wk than the bare metal group at 2 and 4 weeks (20.5 ± 10.7%, 2 wk, p < 0.003; 37.4 ± 20.6%, 4 wk, p < 0.0004). Organized tissues that formed around the coils coated with simvastatin were characterized by an accumulation of cells positive for αSMA and collagen connective matrix. Tissues also were accompanied by marked formation of endothelium at the orifice of the ECA sac. We suggest that coating coils with simvastatin effectively accelerated organization within the aneurysms and endothelialization over the coil. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part 2013.
    Journal of Biomedical Materials Research Part B Applied Biomaterials 01/2013; · 2.31 Impact Factor
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    ABSTRACT: Activation of the thrombotic and complement systems is the main recognition and effector mechanisms in the multiple adverse biological responses triggered when biomaterials or therapeutic cells come into blood contact. We have created a surface which is auto-protective to human innate immunity by combining three fundamentally different strategies, all developed by us previously, which have been shown to induce substantial, but incomplete hemocompatibility when used separately. In summary, we have conjugated a factor H-binding peptide; and an ADP-degrading enzyme; using a PEG linker on both material and cellular surfaces. When exposed to human whole blood, factor H was specifically recruited to the modified surfaces and inhibited complement attack. In addition, activation of platelets and coagulation was efficiently attenuated, by degrading ADP. Thus, by inhibiting thromboinflammation using a multicomponent approach, we have created a hybrid surface with the potential to greatly reduce incompatibility reactions involving biomaterials and transplantation.
    Biomaterials 11/2012; · 7.60 Impact Factor
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    ABSTRACT: Oligonucleotide-based membrane inserts can be used as tethers to control attachment of cells to patterned surfaces without interfering with internal cytoskeletal modes of adhesion. Such control can be employed as a means for study of cell-cell interactions or side-by-side co-culture of different cell types without separation/sorting. While there is utility for cell patterning methods decoupled from natural cytoskeletal mechanisms, the consequences of maintaining this artificially induced state of attachment remains unexplored. We present a method for the 2-dimensional patterning of cells via hybridization of membrane-tethered single stranded oligonucleotides to complimentary single stranded oligonucleotides bound to optically transparent glass substrates which allowed us to characterize the long term culture of patterned HEK293 cells. Patterned substrates immersed in FBS-containing media are shown to permit the adsorption of adhesive serum proteins which allowed for the spreading and engagement of natural cytoskeletal adhesion modes in cells initially attached only through DNA hybridization. We show that the coexisting modes of attachment result in competition between membrane-bound tethers and natural cytoskeletal adhesion machinery as cells attempt to migrate away from their initial points of attachment. This competition ends in the escape of cells from their designated patterns and the 'winning out' of cytoskeletal migration forces over the affinity of lipid inserts for the cell membrane.
    Biomaterials 10/2012; · 7.60 Impact Factor
  • Nguyen Minh Luan, Hiroo Iwata
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    ABSTRACT: Strong immunological reactions remain a major barrier to treating diabetic patients using xenogeneic islets. In a previous study, we developed a method for enclosing islets with agarose microbeads carrying soluble complement receptor 1 (sCR1-Mics), a potent complement inhibitor in both classical and alternative complement activation pathways. This is the follow-up in vivo study to evaluate the protective effect of these sCR1-Mics using a xenotransplantation model (rats to mice). ACI/NSIc rat islets enclosed in sCR1-Mics were transplanted into the intraperitoneal cavity of diabetic C57BL/6 mice without immunosuppression therapy. Transplantation of islets in plain agarose microbeads (Mics) was used as a reference. While islets enclosed in plain Mics were rapidly destroyed (graft survival in recipients of 1000 islets: 11.6±3.8 days), transplantation of islets in sCR1-Mics significantly prolonged graft survival (34.1±3.2 days). Moreover, intraperitoneal glucose tolerance tests revealed that islets in sCR1-Mics normalized blood glucose levels in a similar manner as islets in pancreas of normal mice. In conclusion, sCR1 immobilized onto agarose microbeads exerted some protective effect in xenogeneic islets resulting in prolonged graft survival.
    Biomaterials 08/2012; 33(32):8075-81. · 7.60 Impact Factor
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    ABSTRACT: The purpose of the present study was to determine whether in vivo electroporation could achieve selective blockade of apoptosis in a rat liver cirrhosis model. A dimethylnitrosamine (DMN)-induced rat liver cirrhosis model was used. In vivo electroporation was performed after portal vein infusion of plasmid DNA. pFas-Fc plasmid DNA was used to block the apoptotic pathway. pUC/HGF and pCAGGS/EGFP were used as positive and negative controls, respectively. Liver collagen content was evaluated by hydroxyproline assay two weeks after gene transfer. Terminal deoxynucleotidyltransferase dUTP nick end-labeling was simultaneously performed in the liver to evaluate suppression of apoptosis. Survival analysis was performed using 10 rats that received the sFas gene, 10 that received the HGF gene, and 13 that received the GFP gene. The apoptotic cell index in the DMN-injected liver was significantly lower in rats that received the sFas gene compared with the negative control. The collagen content of the DMN-injected liver was also lower in rats that received the sFas gene compared with the negative control. There was no significant difference in the apoptotic cell index and collagen content of rats that received the sFas and HGF genes. Ten weeks after the initiation of DMN treatment, the survival rates with the sFas, HGF, and GFP genes were 56%, 100%, and 0, respectively. Selective blockade of apoptosis by in vivo electroporation-mediated gene transfer improved the apoptotic cell index, hydroxyproline content, and survival rate. Soluble Fas gene therapy using in vivo electroporation can be a safe and efficient therapy for liver cirrhosis in rats.
    Minerva chirurgica 06/2012; 67(3):249-55. · 0.39 Impact Factor
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    ABSTRACT: Surface plasmon field-enhanced fluorescence spectroscopy (SPFS) combines enhanced field platform and fluorescence detection. Its advantages are the strong intensity of the electromagnetic field and the high signal/noise (S/N) ratio due to the localized evanescent field at the water/metal interface. However, the energy transfer from the fluorophore to the metal surface diminishes the fluorescence intensity, and this reduces the sensitivity. In this study, we tested whether polystyrene (PSt) could act as a dielectric layer to suppress the energy transfer from the fluorophore to the metal surface. We hypothesized that this would improve the sensitivity of SPFS-based immunoassays. We used α-fetoprotein (AFP) as a model tumor biomarker in the sandwich-type immunoassay. We determined the relationship between fluorescent signal intensity and PSt layer thickness and compared this to theoretical predictions. We found that the fluorescence signal increased by optimally controlling the thickness of the PSt layer. Our results indicated that the SPFS-based immunoassay is a promising clinical diagnostic tool for quantitatively determining the concentrations of low-level biomarkers in blood samples.
    Analytical Biochemistry 02/2012; 421(2):632-9. · 2.58 Impact Factor
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    ABSTRACT: Cell transplantation is a potential methodology for the treatment of Parkinson's disease. However, the therapeutic effect is limited by poor viability of transplanted cells. To overcome this problem, we hypothesized that a dual step approach, whereby providing an adhesive substrate for transplanted cells and, at the same time, by preventing the infiltration of activated microglia into the site of transplantation promotes the cell survival. To establish above conditions, attempts were made to prepare 3-D matrices using collagen hydrogels that incorporated integrin-binding polypeptides derived from laminin-1. Tandem combinations of laminin globular domains as well as a single globular domain 3 were prepared using recombinant DNA technology as a fusion with hexahistidine and bound to metal chelated surfaces to screen for the adhesion and proliferation of neural stem cells (NSCs). In addition, a small peptide derived from laminin γ1 chain was prepared and heterodimerized with the globular domain-containing chimeric proteins to evaluate for the enhancement of integrin-mediated cell adhesion. As a result, a heterodimer consisting of the globular domain 3 of the laminin α1 chain and the peptide from the laminin γ1 chain was selected as the best candidate among the polypeptides studied here for the incorporation into a collagen hydrogel. It was shown that the survival of NSCs was indeed promoted in the collagen hydrogel incorporating the heterodimer compared to the pure collagen hydrogel.
    Bioconjugate Chemistry 02/2012; 23(2):212-21. · 4.58 Impact Factor
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    ABSTRACT: Hepatocyte-based therapies are promising regenerative approaches for liver diseases. In this study, we sought to develop a versatile method to modify the surface of hepatocytes by immobilizing synthetic polymers around the cells. The surface of murine primary hepatocytes was modified using poly(ethylene glycol)-phospholipids conjugate bearing FITC (FITC-PEG-lipid) in suspension. Hepatocyte function was assessed in vitro by examining cell viability, plating efficiency, protein production, metabolizing activity, hepatocyte-specific gene expressions, and cytochrome P450 induction. The engraftment of the PEG-lipid modified cells was studied following transplantation to both the liver or alternate ectopic sites. Among the types of phospholipids analyzed in our study, 1,2-dimyristoil -sn-glycerol-3-phosphatidylethanolamine (DMPE) was found to be uniformly anchored to the hepatocyte cell membrane (>99% of hepatocytes). Cell surface modification using FITC-PEG-DMPE did not result in any loss of in vitro functional parameters nor affect the engraftment potential in vivo by the modified cells. This modification was also successfully performed on dispersed hepatocytes and engineered hepatocyte sheets. In all, the ability to modify the surface of isolated hepatocytes with functional proteins, instead of FITC as shown in our proof-of-concept study, has the potential to move hepatocyte-based cell therapy another step forward as a viable therapeutic application.
    Biomaterials 01/2012; 33(3):821-8. · 7.60 Impact Factor
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    ABSTRACT: We aimed to establish a culture system of human pluripotent stem cells (hPSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), free from xenogeneic proteins, Matrigel(™) and conditioned medium of mouse embryonic fibroblasts. The conditioned culture medium consisted of mesenchymal stem cells derived from human bone marrow. We examined surface properties suitable for hPSC culture by using self-assembled monolayers (SAMs) of alkanethiols with four different functional groups: CH(3), OH, COOH and NH(2). hPSCs neither adhered nor proliferated on surfaces with a water contact angle higher than 40°. Based on this finding, the contact angle of a polystyrene (PSt) culture dish was reduced to less than 40°, and COOH and OH groups were introduced to its surface by oxygen plasma treatment, making the PSt dish suitable for hPSC culture. This combination of a PSt dish treated with oxygen plasma treatment and conditioned medium of mesenchymal stem cells achieved a long-term maintenance of hPSCs without differentiation.
    Journal of Biomaterials Science Polymer Edition 01/2012; 23(1-4):153-65. · 1.70 Impact Factor
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    ABSTRACT: Pneumothorax, defined as the presence of air in the pleural space, is usually classified as spontaneous or traumatic; it is unusual for pneumothorax to be categorized as being acute or chronic. Even if conservative treatment is chosen, the pneumothorax is cured when air in the pleural space dissolves into the venous blood. A 50-years-old Japanese man with no prior medical history was referred to our department with a right pneumothorax and two rightsided pulmonary nodules on chest X-ray and CT. The chest radiographs of past mass screening which was taken four years ago showed right pneumothorax and right-sided pulmonary nodules. From then, all chest radiograph and chest computed tomography showed right pneumothorax and pulmonary nodules. But he underwent no medical interventions. We designed to perform an operation for a treatment of right pneumothorax and the diagnosis of pulmonary tumors. We underwent right upper lobectomy and pleural decortication under video assisted thoracic surgery. We obtained pathological diagnosis of inflammatory pseudotumor and surrounding atelectasis. He was cured from pneumothorax and pulmonary tumors. A unique case of spontaneous pneumothorax presenting with a pleural air space that was confirmed by chest radiographs and computed tomography examinations over a 4-year period is reported.
    Prague medical report 01/2012; 113(4):303-208.
  • Hao Chen, Yuji Teramura, Hiroo Iwata
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    ABSTRACT: An unresolved obstacle in transplantation of islets of Langerhans is the early graft loss caused by thrombotic reactions on the surface of islets after intraportal transplantation. We investigated a versatile method for modifying the surface of islets with liposomes carrying the anticoagulant argatroban using an amphiphilic poly(ethylene glycol)-phospholipid conjugate derivative (PEG-lipid) and DNA hybridization. Argatroban was gradually released from the liposomes on the islets, and antithrombic activity was detected in culture medium. Modified islets retained the ability to control insulin release in response to glucose concentration changes. Although we mainly examined surface modification of islets, this technique may be useful for immobilizing various types of small molecules on cells and tissues and thus may have many applications in cell therapy and regenerative medicine.
    Biomaterials 11/2011; 32(31):7971-7. · 7.60 Impact Factor

Publication Stats

4k Citations
1,088.33 Total Impact Points

Institutions

  • 1991–2013
    • Kyoto University
      • • Institute for Frontier Medical Sciences
      • • Graduate School of Engineering / Faculty of Engineering
      • • Graduate School of Medicine / Faculty of Medicine
      • • Department of Neurosurgery
      Kyoto, Kyoto-fu, Japan
  • 2003–2012
    • Gifu University
      • • Graduate School of Medicine
      • • Department of General and Cardiothoracic Surgery
      Gihu, Gifu, Japan
    • University of Rajshahi
      Rampur Baolia, Rājshāhi, Bangladesh
  • 2010
    • Kanazawa University
      • Department of Neurosurgery
      Kanazawa, Ishikawa, Japan
    • Donghua University
      Shanghai, Shanghai Shi, China
  • 2005–2008
    • Mie University
      • Department of Neurosurgery
      Tsu-shi, Mie-ken, Japan
  • 1998–2007
    • Nara Medical University
      • • Department of Surgery
      • • Department of Radiology
      Nara-shi, Nara, Japan
    • Kinki University
      • Department of Surgery
      Ōsaka-shi, Osaka-fu, Japan
  • 2004–2005
    • University of Geneva
      • Division of Radio-oncology
      Genève, GE, Switzerland
  • 1999–2003
    • Gifu University Hospital
      Gihu, Gifu, Japan
  • 1993–1999
    • Nagoya City University
      • • Division of Breast and Endocrine Surgery
      • • Department of Surgery
      Nagoya, Aichi, Japan
    • Hamamatsu Rosai Hospital
      Hamamatu, Shizuoka, Japan
  • 1985–1998
    • National Cerebral and Cardiovascular Center
      • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan