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

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

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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

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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： Cell sheet Endoscopic resection Esophagealstenosis Oral mucosa Good manufacturing practice

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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 esophagus. However, the large defects in the esophageal mucosa often cause severe esophageal strictures, which dramatically reduce the patient’s quality of life. Although preventive endoscopic balloon dilatation can reduce dysphagia and the frequency of dilatation, other approaches are necessary to prevent esophageal strictures after ESD. This review describes several strategies for preventing esophageal strictures after ESD, with a particular focus on anti-inflammatory and tissue engineering approaches. The local injection of triamcinolone acetonide and other systemic steroid therapies are frequently used to prevent esophageal strictures after ESD. Tissue engineering approaches for preventing esophageal strictures have recently been applied in basic research studies. Scaffolds with temporary stents have been applied in five cases, and this technique has been shown to be safe and is anticipated to prevent esophageal strictures. Fabricated 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 ulcers. Fabricated autologous oral-mucosal-epithelial cell sheets have already been shown to be safe.

关键词： Endoscopic submucosal dissection Esophageal stricture Systemic steroid therapy Autologous oral mucosal epithelial cell sheet

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Fatigue sensation following peripheral viral infection is triggered by neuroinflammation: who will answer these questions?

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Neural Regeneration Research 2015年第2期10卷 203-204页

作者： Masanori yamato Yosky Kataoka Cellular Function Imaging Team RIKEN Center for Life Science Technologies

Fatigue is best defined as difficulty in initiating or sustaining voluntary activities, and is thought to be accompanied by deterioration of performance. Fatigue can be caused by many factors such as physical and mental stress, disturbance in the circadian rhythm, and various diseases. For example, following the flu or other types of infections, everyone has experienced a sense of fatigue that can last for days or weeks. The fatigue sensation is thought to be one of the signals for the body to suppress physical activity in order to regain health. The mechanism of induction of the fatigue sensation following viral infection has not been well understood. Although fatigue was once thought to be caused by fever, our recent study with an animal model of viral infection demonstrated that the fatigue sensation is caused not by fever, but rather,

关键词： who will answer these questions will

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Fast-moving bimorph actuator based on electrochemically treated millimeter-long carbon nanotube electrodes and ionic liquid gel

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International Journal of Smart and Nano Materials 2012年第4期3卷 263-274页

作者： Kentaro yamato Ken Mukai Kenji Hata Kinji Asaka Health Research Institute National Institute of Advanced Industrial Science and Technology(AIST)1-8-31 MidorigaokaIkedaOsaka 563-8577Japan Nanotube Research Center National Institute of Advanced Industrial Science and Technology(AIST)Central 51-1-1 HigashiTsukubaIbaraki 305-8565Japan

The development is described of an electromechanical bimorph actuator composed of ionic liquid gel sandwiched by electrochemically treated millimeter-long single-walled carbon nanotubes(SG-SWNT).Electrochemical doping of the SG-SWNT and electrochemical polymerization of polypyrrole on the surface of the SG-SWNT improved the performance of a previously reported actuator using non-treated *** conductivity of the SG-SWNT sheets treated at the anodic potential(doped)was found to be three times larger than that of the original *** generated strain of the actuator prepared from the doped SG-SWNT sheets was increased compared to that prepared from non-doped ***,the generated strain of the actuator from the doped SG-SWNT sheets swelled with ionic liquid(IL)was increased to twice that without *** electropolymerization of pyrrole on the surface of the SG-SWNT sheet was carried *** conductivity of the SG-SWNT was seven times larger after the *** generated strain of the SG-SWNT actuator prepared from the SG-SWNT sheets with electropolymerization was twice as large as that without the electropolymerization at low *** higher frequency,both actuators provide almost the same *** actuators exhibit mechanical resonance at about 100 Hz.

关键词： carbon nanotube polypyrrole electrochemical doping ionic liquid bimorph actuator

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Synthesis and fluorescence properties of a 1,3-disubstituted thiacalix[4]arene crown-5 armed with phenothiazine moieties

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Science China Chemistry 2015年第3期58卷 539-544页

作者： Qiang Sun Lan Mu Xi Zeng Jianglin Zhao Takehiko yamato Jianxin Zhang Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province Guizhou University Department of Applied Chemistry Faculty of Science and Engineering Saga University Honjo-machi 1 Saga-shi Saga 840-8502 Japan The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences

A new thiacalix[4]arene phenothiazine derivative(2) based on a thiacalix[4]crown with a 1,3-alternate conformation has been synthesized and characterized. In THF-water mixture, Compound 2 exhibits a strong fluorescence emission, with a large Stokes shift(λex/em = 357 nm/505 nm, Δλ = 148 nm), which helps to avoid interference in excitation and emission. For the metal ions tested, the fluorescence of Compound 2 was quenched only by Fe3+ and Cr3+ ions. Evidence for the hydrolysis reaction promoted by the metal ions is given by X-ray crystallography, mass spectra(MS), infrared(IR) spectra, and fluorescence spectroscopy data.

关键词： thiacalixcrown phenothiazine Fe3+ and Cr3+ hydrolysis reaction

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IBX Oxidation of Benzenedimethanols in the Presence of Cucurbit[8]uril

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Chinese Journal of Chemistry 2015年第5期33卷 545-549页

作者： Hang Cong Qiuju Chen Qingxia Geng Zhu Tao Takehiko yamato Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province Guizhou UniversityGuiyangGuizhou 550025China Department of Applied Chemistry Faculty of Science and EngineeringSaga UniversityHonjo-machilSaga 840-8502Japan

The cucurbit[8]uril (Q[8]) mediated oxidation of benzenedimethanols with o-iodoxybenzoic acid (IBX) inaqueous solution has been investigated, and the results reveal the supramolecular catalysis depends on the electronicand geometric structure of substrate. In the cases of o-benzenedimethanol (1a) and m-benzenedimethanol (1b), theIBX oxidation could be obviously enhanced by the addition of Q[8] at different extent. There is no observation ofthe catalytic activity of Q[8] when p-benzenedimethanol (1c) is subjected to the IBX oxidation. The additionamount of Q[8] is discussed herein, and the addition of more than 10% mol catalyst cannot improve the oxidationmuch more. The investigation of host-guest interactions by isothermal titration calorimetry implies the supramolecularcatalysis is related to the formation of complexes between benzenedimethanols and cucurbit[8]uril.

关键词： cucurbituril oxidation supramolecular catalysis benzenedimethanol o-iodoxybenzoic acid

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Integrated in-process chatter monitoring and automatic suppression with adaptive pitch control in parallel turning

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Advances in Manufacturing 2018年第3期6卷 291-300页

作者： Shuntaro yamato Yuki Yamada Kenichi Nakanishi Norikazu Suzuki Hayato Yoshioka Yasuhiro Kakinuma Department of System Design Engineering Keio University3-14-1 Hiyoshi Kohoku-ku Yokohama 223-8522 Japan Nakamura-Tome Precision Industry Co. Ltd. 15 NetsunoHakusan Ishikawa 920-2195 Japan Department of Mechanical Science and Engineering Nagoya University Furo-cho Chikusa-ku Nagoya 464-8603 Japan Precision and Intelligent Laboratory Tokyo Institute of Technology 4259-G2-19 Nagatsuta Midori-kuYokohama 226-8503 Japan

Simultaneous processes such as parallel turningor milling offer great opportunities for more efficientmanufacturing because of their higher material removalrates. To maximize their advantages, chatter suppressiontechnologies for simultaneous processes must be devel-oped. In this study, we constructed an automatic chattersuppression system with optimal pitch control for shared-surface parallel turning with rigid tools and a flexibleworkpiece, integrating in-process chatter monitoring basedon the cutting force estimation. The pitch angle betweentwo tools is tuned adaptively in a position control system inaccordance with the chatter frequency at a certain spindlespeed, in a similar manner as the design methodology forvariable-pitch cutters. The cutting force is estimatedwithout using an additional external sensor by employing amulti-encoder-based disturbance observer. In addition, thechatter frequency is measured during the process by per-forming a low-computational-load spectrum analysis at acertain frequency range, which makes it possible to cal-culate the power spectrum density in the control system ofthe machine tool. Thus, the constructed system for automatic chatter suppression does not require any addi-tional equipment.

关键词： Chatter Multitasking machine tool Parall elturning Adaptive control Sensorless Disturbance observer

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Three cases of retroperitoneal schwannoma diagnosed by EUS-FNA

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World Journal of Gastroenterology 2011年第29期17卷 3459-3464页

作者： Taiki Kudo Hiroshi Kawakami Masaki Kuwatani Nobuyuki Ehira Hiroaki yamato Kazunori Eto Kanako Kubota Masahiro Asaka Department of Gastroenterology Hokkaido University Graduate School of MedicineKita 15Nishi 7Kita-kuSapporo060-8638Japan Department of Surgical pathology Hokkaido University HospitalKita 14Nishi 5Kita-kuSapporo060-8638Japan

Schwannomas are peripheral nerve tumors that are typically solitary and *** diagnosis is largely based on surgically resected ***,a number of case reports have indicated that retroperitoneal schwannomas could be diagnosed with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).We report the diagnosis of three cases of schwannoma using *** were two males and one female,ages 22,40,and 46 years,respectively,all of whom were *** findings showed well-circumscribed round ***,as the tumors could not be diagnosed using these findings alone,EUS-FNA was ***-eosin staining of the resulting tissue fragments revealed bland spindle cells with nuclear *** was no disparity in nuclear *** revealed S-100 protein positivity and all cases were diagnosed as ***-67 indexes were 3%-15%,2%-3%,and 3%,*** case showed any signs of *** most schwannomas are benign tumors and seldom become malignant,we observed these patients without *** tumors demonstrated no enlargement and no change in *** are almost always benign and can be observed following diagnosis by EUS-FNA.

关键词： Schwannoma Endoscopic ultrasonography Fine-needle aspiration Retroperitoneal tumor S100 proteins Ki-67 index

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