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Cell sheet technology for regeneration of esophageal mucosa

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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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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