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Regenerative medicine of cornea by cell sheet engineering using temperature-responsive culture surfaces

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Chinese Science Bulletin 2013年第35期58卷 4349-4356页

作者： UMEMOTO Terumasa YAMATO Masayuki NISHIDA Kohji okano teruo Institute of Advanced Biomedical Engineering and Science Tokyo Women’s Medical University Tokyo 162-8666 Japan Department of Ophthalmology Osaka University Medical School Osaka 565-0871 Japan

Recently,regenerative medicine has been focused on as next-generation definitive therapies for several diseases or injuries for which there are currently no effective *** therapies have been rapidly developed through the effective fusion between different fields such as stem cell biology and *** far,we have proposed"cell sheet engineering"through our core technology that simply applies alterations of the temperature which allows regulation of the attachment or detachment of living cells on the culture surfaces grafted with the temperature-responsive polymer"poly(N-isoproplyacrylamide)".This technology enables us to construct bioengineered sheet-like tissues,termed"cell sheets",without the need of using biodegradable scaffolds and protease treatments that are traditionally ***,our carrier-free cell sheets not only are independent of the issues observed in conventional methods,but also showed further advantages in the reconstruction of the corneal epithelium or endothelium(*** of optical transparency and cell-cell interactions to host stroma in reconstructed tissues).Moreover,our approach does not have issues such as immune rejection or limited number of donors,due to the use of cell sheets derived from autologous limbal(in patients with unilateral disease)or oral mucosal epithelial cells(in patients with bilateral disorders).Indeed,we have successfully performed the clinical application for the reconstruction of ocular surfaces through the transplantation of our carrier-free corneal epithelial cell sheets,as evidenced by improved visual acuity as well as long-term maintenance of postoperative health conditions on ocular surfaces in all *** have also proposed a novel approach for the reconstruction of the corneal endothelium using corneal endothelial cell sheets by demonstrating its successful ***,our cell sheet engineering technique provides a breakthrough in the field of regenerative medicine appli

关键词：干细胞生物学角膜上皮表面重建再生医学调节温度工程化反应性角膜内皮细胞

Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia

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World Journal of Gastroenterology 2009年第42期15卷 5307-5315页

作者： Kohei Tatsumi Kazuo Ohashi Sanae Taminishi Soichi Takagi Rie Utoh Akira Yoshioka Midori Shima teruo okano Institute of Advanced Biomedical Engineering and Science Tokyo Women's Medical University8-1 Kawada-choShinjuku-kuTokyo 162-8666Japan Department of Pediatrics Nara Medical Univrsity840 Shijo-choKashiharaNara 634-8522Japan

AIM:To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia(DH) -mediated liver ***:Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bis[2-(3,5-dichloropyridyloxy) ] benzene(TCPOBOP) ,a representative *** were weighed and sacrificed at various time points [Day 0(D0:prior to injection) ,3 h,D1,D2,D3,and D10] after TCPOBOP administration to obtain liver and blood *** the RNA samples extracted from the liver,a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR(fibrinogen,prothrombin,factors Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅹ,Ⅺ,Ⅻ,XⅢβ,plasminogen,antithrombin,protein C,protein S,ADAMTS13,and VWF) .The corresponding plasma levels of coagulation factors(fibrinogen,prothrombin,factors Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅹ,Ⅺ,Ⅻ,XⅢ,and VWF) were also analyzed and compared with their mRNA ***:Gavage administration of TCPOBOP(3 mg/kg body weight) resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the D0(control) *** the peak of liver regeneration(D1 and D2) ,the gene expression levels for most of the coagulationrelated factors(fibrinogen,prothrombin,factors Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅺ,Ⅻ,XⅢβ,plasminogen,antithrombin,protein C,ADAMTS13,VWF) were found to be downregulated in a time-dependent manner,and gradually recovered by D10 to the basal *** mRNA levels of factor Ⅹ and protein S failed to show any decrease during the regenerative *** for the plasma levels,5 clotting factors(prothrombin,factors Ⅷ,Ⅸ,Ⅺ,and Ⅻ) demonstrated a significant decrease(P < 0.05) during the regeneration phase compared with *** these 5 factors,factor Ⅸ and factor Ⅺ showed the most dramatic decline in their activities by about 50% at D2 compared to the basal levels,and these reductions in plasma activity for both factors

关键词：肝疾病增生临床治疗

Cell sheet technology for regeneration of esophageal mucosa

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World Journal of Gastroenterology 2012年第37期18卷 5145-5150页

作者： Ryo Takagi Masayuki Yamato Nobuo Kanai Daisuke Murakami Makoto Kondo Takaaki Ishii Takeshi Ohki Hideo Namiki Masakazu Yamamoto teruo okano Institute of Advanced Biomedical Engineering and Science Tokyo Women's Medical University Department of Surgery Institute of GastroenterologyTokyo Women's Medical University Graduate School of Science and Engineering Waseda University

The progress of tissue-engineering technology has realized development of new therapies to treat various disorders by using cultured cells. Cell-and tissue-based therapies have been successfully applied to human patients, and several tissue-engineered products have been approved by the regulatory agencies and are commercially available. In the review article, we describe our experience of development and clinical application of cell sheet-based regenerative *** mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been shown to be useful for removal of gastrointestinal neoplasms with less invasiveness compared with open surgery, especially in esophageal surgery. However, postoperative inflammation and stenosis are major complications observed after intensive mucosal resection. Therefore, we have developed novel regenerative medicine to prevent such complications and promote wound healing of esophageal mucosa after EMR or ESD. Transplantable oral mucosal epithelial cell sheets were fabricated from patients' own oral mucosa. Immediately after EMR or ESD, fabricated autologous cell sheets were endoscopically transplanted to the ulcer sites. We performed a preclinical study with a canine model. In human clinical settings, cell culture and cell sheet fabrication were performed in clean rooms according to good manufacturing practice guidelines, and pharmaceutical drugs were used as supplements to culture medium in place of research regents used in animal study. We believe that cell-based regenerative medicine would be useful to improve quality of life of patients after EMR or ESD.

关键词：口腔黏膜食管癌再生技术电池板上皮细胞临床应用再生医学胃肠道肿瘤

Cell sheet therapy for myocardial infarction

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岭南心血管病杂志 2011年第S1期17卷 23-24页

作者： Dehua Chang Tatsuya Shimizu teruo okano Institute of Advanced Biomedical Engineering and Science Tokyo Women's Medical University

Introduction Recently,bone marrow mesenchymal stem cells(MSCs) have been reported to repair chronically infracted myocardium with direct ***,it is very difficult to localize the injected cells onto the ischemic area to regenerate sufficient cardiac mass in the thinned scar *** overcome the problem,we have utilized our cell sheet technology based on temperature-responsive culture *** the culture temperature is reduced from 37℃to 20℃,all cells connected via cell-cell junction proteins are harvested as a single sheet without using proteolytic *** technology allows us to transplant stem cells in vivo for treatment heart disease without the problems mention in the *** Male Clawn mini pigs were used in this *** marrow(5-7 mL)was collected under general anesthesia. Histopaqe-1077(15 mL),were added to bone marrow and *** cells were collected and cultured for 7 *** seeded the bone marrow-derived MSCs at the concentration of(6×10~5/ml) on 60 mm diameter temperature -responsive dishes for 7 *** the culture temperature decreased from 37℃to 20℃,MSC sheet detached itself spon-taneously and floated up into the culture medium. Triple layers were stacked together repeatedly forming special *** infarction was created by the ligation of the left anterior descending branch of the left coronary artery.A cell sheets was transplanted onto the ischemia *** echocardiography was performed two and four weeks after *** heart tissue with cell sheets were removed and fixed with 10%formalin for histological analysis one month after the transplantation of cell *** Most MSCs are positive for CD29,CD90,CD146 and *** mean the culture cell sheets were composed of undifferentiated MSCs and remained ***(20- 30μm) and multilayer(120μm) cell sheets were produced,which retained all cell-to-cell contaction. Histological analyses show the cell sheets become c

关键词： sheet descending myocardium anesthesia transplant responsive multilayer overcome powerful created

Novel isolated cecal pouch model for endoscopic observation in rats

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World Journal of Gastroenterology 2015年第17期21卷 5242-5249页

作者： Kurodo Koshino Nobuo Kanai Masayuki Yamato teruo okano Masakazu Yamamoto Institute of Gastroenterology School of SurgeryTokyo Women’s Medical UniversityShinjuku-kuTokyo 162-8666Japan Institute of Advanced Biomedical Engineering and Science Tokyo Women’s Medical UniversityShinjuku-kuTokyo 162-8666Japan

AIM:To create a new rat model for drug administration,cell transplantation,and endoscopic examination for the treatment of intestinal ***:F344/NJc l-rnu/rnu rats(10-wk-old males,350-400 g) were used in this *** rats were anesthetized via 2% isoflurane *** rat's cecum was isolated from the intestines,and a pouch was *** remainder of the intestines was rejoined to create an *** "side-to-side" anastomosis(SSA) technique initially involves the creation of a 2-cm longitudinal incision into each intestinal *** create an anastomosis along the ileal and colonic walls,both intestines were cut,and a continuous suture procedure was performed that included all layers of both *** serous membrane was sutured along the edge and on the anterior wall of the *** "end-toend" anastomosis(EEA) technique was compared with the SSA *** the EEA technique,the frontal surfaces of both cut intestinal lumens were joined together by continuous *** sutures were made at the *** the anastomotic intestine was successfully constructed,the two intestinal lumens that were cut at the isolated cecum were *** addition,one luminal side of the pouch remained open to create an artificial anus on the dorsum as a passage for the residual substances in the ***,small animal endoscopy was used to observe the inside of the ***:In this animal model,mucus and feces are excreted through the reconstructed ***,the cecal pouch mucosa was not obstructed or contaminated by feces,thus facilitating observations of the luminal surface of the *** endoscopic observation of the cecal pouch provided clear visualization given the absence of *** membrane surface of the cecum was clearly *** methods of creating an anastomotic intestine,the "SSA" and "EEA" techniques,were compared with regard to animal survival rate,complication rate,and operation *** S

关键词： Animal model Anastomosis Endoscopy Cecal pouch Microsurgery

Neutral Pion Electromagnetic Form Factor as a Bound System of 3 + 1 Dimensional QCD

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Journal of Modern Physics 2024年第7期15卷 1036-1044页

作者： teruo Kurai 1-19-18-503 Unoki Ohta-ku Tokyo Japan

We investigate a neutral pion electromagnetic form factor in momentum space and obtain Gaussian-like function for it. The characteristic form of our neutral pion electromagnetic form factor is consistent with the resu... 详细信息

关键词： Neutral Pion Electromagnetic Form Factor Gaussian-Like Function

Prevention of esophageal strictures after endoscopic submucosal dissection

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World Journal of Gastroenterology 2014年第41期20卷 15098-15109页

作者： Shinichiro Kobayashi Nobuo Kanai Takeshi Ohki Ryo Takagi Naoyuki Yamaguchi Hajime Isomoto Yoshiyuki Kasai Takahiro Hosoi Kazuhiko Nakao Susumu Eguchi Masakazu Yamamoto Masayuki Yamato teruo okano Institute of Advanced Biomedical Engineering and Science Tokyo Women’s Medical University Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Department of Surgery Institute of GastroenterologyTokyo Women’s Medical University Department of Gastroenterology and Hepatology Nagasaki University Graduate School of Biomedical Sciences Graduate School of Advanced Science and Engineering Life Science and Medical BioscienceWaseda University Department of Pharmaceutical Sciences Graduate School of Pharmaceutical SciencesTokyo University of Science

Endoscopic mucosal resection(EMR) and endoscopic submucosal dissection(ESD) have recently been accepted as less invasive methods for treating patients with early esophageal cancers such as squamous cell carcinoma and dysplasia of Barrett's ***,the large defects in the esophageal mucosa often cause severe esophageal strictures,which dramatically reduce the patient's quality of *** preventive endoscopic balloon dilatation can reduce dysphagia and the frequency of dilatation,other approaches are necessary to prevent esophageal strictures after *** review describes several strategies for preventing esophageal strictures after ESD,with a particular focus on anti-inflammatory and tissue engineering *** local injection of triamcinolone acetonide and other systemic steroid therapies are frequently used to prevent esophageal strictures after *** engineering approaches for preventing esophageal strictures have recently been applied in basic research *** with temporary stents have been applied in five cases,and this technique has been shown to be safe and is anticipated to prevent esophageal *** autologous oral mucosal epithelial cell sheets to cover the defective mucosa similarly to how commercially available skin products fabricated from epidermal cells are used for skin defects or in cases of intractable *** autologous oralmucosal-epithelial cell sheets have already been shown to be safe.

关键词： Endoscopic submucosal dissection Esophageal strict

PEO coating on Mg-Ag alloy:The incorporation and release of Ag species

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镁合金学报(英文) 2023年第6期11卷 2182-2195页

作者： Xinxin Zhang Yupeng Zhang You Lv Zehua Dong Lei Yang Erlin Zhang teruo Hashimoto Xiaorong Zhou Key Laboratory of Material Chemistry for Energy Conversion and Storage Ministry of EducationHubei Key Laboratory of Material Chemistry and Service FailureSchool of Chemistry and Chemical EngineeringHuazhong University of Science and TechnologyWuhan 430074China Hubei Engineering Research Centre for Biomaterials and Medical Protective Materials Huazhong University of Science and TechnologyWuhan 430074China Key Laboratory for Anisotropy and Texture of Materials Education Ministry of ChinaSchool of Materials Science and EngineeringNortheastern UniversityShenyang 110819China Corrosion and Protection Centre Department of MaterialsThe University of ManchesterManchester M139PLUnited Kingdom

In the present study,the distribution of Ag in the coating formed on Mg-Ag alloy by plasma electrolytic oxidation(PEO)and its ionic release kinetics when exposed to a 0.9 wt.%Na Cl solution at 37℃have been *** metallic Ag and Ag oxide particles with~5 to~40 nm in diameters were observed in the PEO ***,an Ag-enriched layer of~20 nm in thickness at the substrate/coating interface was also *** PEO coating on the Mg-Ag alloy not only increases its corrosion resistance with the corrosion current density decreasing by up to 3 orders of magnitude from 8.04×10^(-3)to 4.03×10^(-6)A/cm^(2),but also controls the release of Ag+to the level that is sufficient for anti-infective efficacy without causing cytotoxicity to mammal cells.

关键词： Mg-Ag alloy Plasma electrolytic oxidation Ag distribution Ag release Corrosion resistance

A New Electron Charge Distribution Function of Electron

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Journal of Modern Physics 2023年第2期14卷 111-126页

作者： teruo Kurai Unoki Ota-ku Tokyo Japan

Here we derive a new charge distribution function for an electron by using as an equation of motion a segment of charge whose self energy interaction is due to electric field potential. Our method is based on the consideration that a charged distribution function should be represented as an eigenfunction of electron mass energy. We compare our electron charge distribution function to that of Weinberg’s η(r) and our charged electron radius to that obtained by Kim.

关键词： Charge Distribution Function Electron