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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

Perivascular localized cells commit erythropoiesis in PDGF-B-expressing solid tumors

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Cancer Communications 2023年第6期43卷 637-660页

作者： Kayoko Hosaka Chenchen Wang Shiyue Zhang Xue Lv Takahiro Seki Yin Zhang Xu Jing Jieyu Wu Qiqiao Du Xingkang He Yulong Fan Xuan Li makoto kondo Masahito Yoshihara Hong Qian Lihong Shi Ping Zhu Yuanfu Xu Yunlong Yang Tao Cheng Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholmSweden State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjinP.R.China Tianjin Institutes of Health Science TianjinP.R.China School of Pharmacology Binzhou Medical UniversityYantaiShandongP.R.China Department of Clinical Laboratory the Second Hospital of Shandong UniversityJinanShandongP.R.China Department of Gastroenterology Sir Run Run Shaw HospitalZhejiang University Medical SchoolHangzhouZhejiangP.R.China Center for Hematology and Regenerative Medicine Department of MedicineKarolinska InstituteKarolinska University HospitalStockholmSweden Department of Biosciences and Nutrition Karolinska InstituteHuddingeSweden Department of Cellular and Genetic Medicine School of Basic Medical SciencesFudan UniversityShanghaiP.R.China

Background:Tumors possess incessant growth features,and expansion of their masses demands sufficient oxygen supply by red blood cells(RBCs).In adult mammals,the bone marrow(BM)is the main organ regulating hematopoiesis with dedicated *** than BM,extramedullary hematopoiesis is discovered in various pathophysiological ***,whether tumors can contribute to hematopoiesis is completely *** evidence shows that,in the tumor microenvironment(TME),perivascular localized cells retain progenitor cell properties and can differentiate into other ***,we sought to better understand whether and how perivascular localized pericytes in tumors manipulate ***:To test if vascular cells can differentiate into RBCs,genome-wide expression profiling was performed using mouse-derived *** tracing of perivascular localized cells employing NG2-CreERT2:R26R-tdTomato mouse strain was used to validate the findings in ***-activated cell sorting(FACS),single-cell sequencing,and colony formation assays were applied for biological *** production of erythroid differentiationspecific cytokine,erythropoietin(EPO),in TME was checked using quantitative polymerase chain reaction(qPCR),enzyme-linked immunosorbent assay(ELISA,magnetic-activated cell sorting and *** investigate BM function in tumor erythropoiesis,BM transplantation mouse models were ***:Genome-wide expression profiling showed that in response to plateletderived growth factor subunit B(PDGF-B),neural/glial antigen 2(NG2)+perivascular localized cells exhibited hematopoietic stem and progenitor-like features and underwent differentiation towards the erythroid ***-B simultaneously targeted cancer-associated fibroblasts to produce high levels of EPO,a crucial hormone that necessitates *** analysis using genetic tracing of NG2+cells in tumors defined the perivascular localized cell-derived sub

关键词： cancer hematopoiesis PDGF-B perivascular localized cell stem cell tumor vasculature

Stage IV malignant transformation of mature cystic teratoma palliatively treated with concurrent chemoradiotherapy:A case report

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World Journal of Clinical Cases 2025年第1期13卷 56-61页

作者： Saori kondo Takashi Suzuki Kanato Yoshiike Sakura Yamanaka Kenta Sonehara Hiroshi Nabeshima Osamu Oguchi Department of Obstetrics and Gynecology Saku Central Hospital Advanced Care CenterSaku City 385-0051NaganoJapan

BACKGROUND Malignant transformation(MT)of mature cystic teratoma(MCT)has a poor prognosis,especially in advanced *** chemoradiotherapy(CCRT)has an inhibitory effect on *** SUMMARY Herein,we present a case in which CCRT had a reduction effect preoperatively.A 73-year-old woman with pyelonephritis was referred to our *** tomography revealed right hydronephrosis and a 6-cm pelvic *** ultrasound-guided fine-needle biopsy(EUS-FNB)revealed squamous cell *** patient was diagnosed with MT of *** to her poor general con-dition and renal malfunction,we selected CCRT,expecting fewer adverse *** CCRT,her performance status improved,and the tumor size was reduced;surgery was *** months postoperatively,the patient developed dis-semination and lymph node *** chemotherapy was *** died 18 months after treatment *** EUS-FNB was useful in the diagnosis of MT of MCT;CCRT suppressed the disea-se and improved quality of life.

关键词： Mature cystic teratoma Malignant transformation Squamous cell carcinoma Concurrent chemoradiotherapy Endoscopic ultrasound-guided fine-needle biopsy Case report

血管周细胞在表达PDGF-B的实体瘤中诱发造血

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癌症 2023年第8期42卷 385-408页

作者： Kayoko Hosaka 王晨晨张诗悦吕雪 Takahiro Seki Yin Zhang Xu Jing Jieyu Wu Qiqiao Du Xingkang He 范玉龙李轩 makoto kondo Masahito Yoshihara Hong Qian 石莉红朱平许元富杨云龙程涛 Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholmSweden 中国医学科学院血液病医院(中国医学科学院血液学研究所) 实验血液学国家重点实验室国家血液系统疾病临床医学研究中心细胞生态海河实验室天津天津医学健康研究院天津 School of Pharmacology Binzhou Medical UniversityYantaiShandongP.R.China Department of Clinical Laboratory the Second Hospital of Shandong UniversityJinanShandongP.R.China Department of Gastroenterology Sir Run Run Shaw HospitalZhejiang University Medical SchoolHangzhouZhejiangP.R.China Center for Hematology and Regenerative Medicine Department of MedicineKarolinska InstituteKarolinska University HospitalStockholmSweden Department of Biosciences and Nutrition Karolinska InstituteHuddingeSweden 复旦大学细胞与遗传医学系上海

背景与目的肿瘤组织持续生长需要红细胞充分供氧。在各类病理生理情况下,成年哺乳动物可在主要造血器官骨髓之外发生髓外造血。然而,肿瘤组织能否造血是完全未知的。大量证据表明,在肿瘤微环境中,血管周细胞保留了祖细胞特性,可分化成... 详细信息

背景与目的肿瘤组织持续生长需要红细胞充分供氧。在各类病理生理情况下,成年哺乳动物可在主要造血器官骨髓之外发生髓外造血。然而,肿瘤组织能否造血是完全未知的。大量证据表明,在肿瘤微环境中,血管周细胞保留了祖细胞特性,可分化成其他细胞类型。在此,我们探究了肿瘤组织内周细胞是否能调节造血及其作用机制。方法使用鼠源周细胞进行全基因组表达谱分析以测试周细胞是否可向红细胞分化。使用NG2-CreERT2:R26R-tdTomato小鼠对血管周细胞进行在体遗传示踪。使用流式细胞术、单细胞测序和集落形成实验对分选细胞进行鉴定。使用定量聚合酶链反应(quantitative polymerase chain reactionq,PCR)、酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)、细胞磁珠分选和免疫染色检查红细胞生成素(erythropoietin,EPO)的表达。构建骨髓移植小鼠模型以研究骨髓对肿瘤红细胞生成的影响。结果表达谱显示,在PDGF-B处理后,NG2+周细胞表现出造血干祖样特征,并向红系谱系分化。同时,PDGF-B可靶向癌症相关成纤维细胞以产生促红细胞生成的关键激素EPO。通过遗传示踪及流式分析,我们定义了NG2+细胞衍生的造血亚群。进一步的单细胞测序和集落形成实验结果显示,在PDGF-B刺激下,肿瘤中的NG2+细胞形成了与典型的骨髓造血干细胞不同的红系祖细胞。结论本研究提出了肿瘤组织内造血的新概念,并阐明肿瘤周细胞分化为红细胞的分子机制。靶向肿瘤造血作为一种新的治疗理念,可能对肿瘤治疗产生深远影响。

关键词：癌症造血 PDGF-B 血管周围细胞干细胞肿瘤血管

Characterization of a microsecond pulsed non-equilibrium atmospheric pressure Ar plasma using laser scattering and optical emission spectroscopy

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Plasma Science and Technology 2020年第6期22卷 120-127页

作者： Fengdong JIA Yong WU Qi MIN Maogen SU Keigo TAKEDA Kenji ISHIKAWA Hiroki kondo makoto SEKINE Masaru HORI Zhiping ZHONG School of Physical Sciences University of Chinese Academy of SciencesBeijing 100049People's Republic of China Institute of Applied Physics and Computational Mathematics Beijing 100088People's Republic of China Key Laboratory of Atomic and Molecular Physics&Functional Material of Gansu Province College of Physics and Electronic EngineeringNorthwest Normal UniversityLanzhou 730070People's Republic of China Department of Electrical and Electronic Engineering Faculty of Science and TechnologyMeijo UniversityNagoya 468-8502Japan Graduate School of Engineering Nagoya UniversityNagoya 464-8603Japan CAS Center for Excellence in Topological Quantum Computation University of Chinese Academy of SciencesBeijing 100190People's Republic of China

A non-equilibrium atmospheric pressure argon(Ar)plasma excited by microsecond pulse is studied experimentally by laser scattering and optical emission spectroscopy(OES),and theoretically by collisional-radiative(CR)*** specifically,the electron temperature and electron density of plasma are obtained directly by the laser Thomson scattering,the gas temperature is measured by laser Raman scattering,the optical emissions of excited Ar states of plasma are measured by *** laser scattering results show that the electron temperature is about 1 eV which is similar to that excited by 60 Hz AC power,but the gas temperature is as low as 300 K compared to about 700 K excited by 60 Hz AC *** is shown that the microsecond pulsed power supply,rather than nanosecond ones,is short enough to reduce the gas temperature of atmospheric pressure plasma to near room *** electron temperature and electron density are also obtained by CR model based on OES,and find that the intensities of the optical emission intensity lines of 727.41,811.73,841.08,842.83,852.44 and 912.86 nm of Ar can be used to characterize the behavior of electron density and electron temperature,it is very useful to quickly estimate the activity of the atmospheric pressure Ar plasma in many applications.

关键词： plasma diagnosis laser Thomson scattering atmospheric pressure plasma

Acquired hemophilia A in solid cancer: Two case reports and review of the literature

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World Journal of Clinical Cases 2018年第14期6卷 781-785页

作者： makoto Saito Reiki Ogasawara Koh Izumiyama Akio Mori Takeshi kondo Masanori Tanaka Masanobu Morioka Masahiro Ieko Department of Internal Medicine and Hematology Aiiku Hospital Department of Internal Medicine Health Sciences University of Hokkaido

Acquired hemophilia A （AHA） is a rare, hemorrhagic autoimmune disease, whose pathogenesis involves reduced coagulation factor Ⅷ （FⅧ） activity related to the appearance of inhibitors against FⅧ. Common etiological factors include autoimmune diseases, ma-lignancy, and pregnancy. We report two cases of AHA in solid cancer. The first case is a 63-year-old man who developed peritoneal and intestinal bleeding after gastrectomy for gastric cancer. He was diagnosed with AHA, and was treated with prednisone, followed by cyclophosphamide. In the second case, a 68-year-old man developed a subcutaneous hemorrhage. He was diagnosed with AHA in hepatocellular carcinoma on CT imaging, and treated with rituximab alone. Hemostasis was achieved for both patients without bypassing agents as the amount of inhibitors was reduced and eradicated. However, both patients died within 1 yeardue to cancer progression. Successful treatment for AHA in solid cancer can be diffcult because treatment of the underlying malignancy is also required.

关键词： Acquired hemophilia A Coagulation factor Ⅷ Solid cancer Gastric cancer Hepatocellular carcinoma Case report

New microsome-associated HT-family proteins from Nicotiana respond to pollination and define an HT/NOD-24 protein family

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Molecular Plant 2008年第4期1卷 634-644页

作者： Katsuhiko kondo Bruce McClure Department of Biochemistry Interdisciplinary Plant Group and the Christopher S. Bond Life Sciences Center University of Missouri MI USA

HT-family proteins have been identified in Nicotiana, Solanum, and Petunia. HT-B-type proteins are implicated in S-RNase-based self-incompatibility, but the functions of other family members are unknown. Screening for cDNA sequences with an expression pattern similar to HT-B in Nicotiana alata revealed a new group of small HT-family proteins, designated HT-M. HT-M proteins resemble HT-B in several respects： their pistil-specific expression pattern is indistinguishable from HT-B, they pellet with a microsome fraction, and their abundance decreases after pollination. Unlike HT-B, there is no S-specificity to this response, and RNAi experiments show that HT-M proteins are not necessary for self-incompatibility. Identification of a third group of pistil-specific HT-family proteins helps better define the characteristics of the family and allowed identification of putative new family members. By searching the databases with only the most conserved HT- family sequence elements, the signal sequence and cysteine motifs, we identified nodulin-24-1ike proteins and several small glycine-rich proteins as putative HT-family members. Like HT-M and HT-B, nodulin-24 is membrane associated. We propose that the conserved features in HT-family proteins are important for targeting or modification and refer to the broader family that includes both HT- and nodulin-24-1ike proteins as the HT/NOD-24-family.

关键词： New microsome-associated HT-family pollination an HT/NOD-24 protein family

ALK-positive anaplastic large cell lymphoma presenting multiple lymphomatous polyposis: A case report and literature review

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World Journal of Clinical Cases 2019年第15期7卷 2049-2057页

作者： makoto Saito Koh Izumiyama Reiki Ogasawara Akio Mori Takeshi kondo Masanori Tanaka Masanobu Morioka Kencho Miyashita Mishie Tanino Department of Internal Medicine and Hematology Aiiku HospitalSapporo 0640804Japan Department of Gastroenterology Aiiku HospitalSapporo 0640804Japan Department of Surgical Pathology Asahikawa Medical University Hospital(formerly Department of Cancer PathologyHokkaido UniversityFaculty of Medicine)Asahikawa 0788510Japan

BACKGROUND Anaplastic large cell lymphoma(ALCL)is a type of T-cell lymphoma that can be divided into two categories:anaplastic lymphoma kinase-positive(ALK+)and *** ALK+ALCL is *** lymphomatous polyposis(MLP)is thought to be a representative form of gastrointestinal lesion in mantle cell lymphoma,and T-cell lymphomas seldom show this ***,we report the first known case of ALK+ALCL with gastroduodenal involvement to present with *** SUMMARY The patient was a 43-year-old man who was complained of a mass in the left inguinal area and was performed open ***+ALCL was diagnosed *** tomography scan demonstrated multiple lymph node lesions in the abdomen-pelvis/inguinal region,and scattered nodular lesions in both lung *** did not complain of gastrointestinal ***,esophagogastroduodenoscopy identified MLP lesions from the antrum of the stomach to the descending portion of the duodenum and mild thickened folds on the corpus of the stomach,and biopsy showed invasion of ALK+*** treated this patient with six cycles of CHOEP(Cyclophosphamide,Doxorubicin,Vincristine,Etoposide,and Prednisone)*** the conclusion of treatment,there was complete *** white scars were found on the stomach,endoscopically consistent with a remission image of *** endoscopic features of this case were thought to be similar to those of *** The macroscopic/endoscopic features of gastrointestinal ALK+ALCL may be more similar to those of B-cell lymphomas rather than T-cell lymphomas.

关键词： Anaplastic large-cell lymphoma Anaplastic lymphoma kinase Multiple lymphomatous polyposis T-cell lymphoma Gastrointestinal involvement

Phlegmonous gastritis developed during chemotherapy for acute lymphocytic leukemia:A case report

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World Journal of Clinical Cases 2021年第22期9卷 6493-6500页

作者： makoto Saito Masanobu Morioka Koh Izumiyama Akio Mori Reiki Ogasawara Takeshi kondo Toru Miyajima Emi Yokoyama Satoshi Tanikawa Department of Internal Medicine and Hematology Aiiku HospitalSapporo 0640804HokkaidoJapan Department of Cancer Pathology Hokkaido UniversityFaculty of MedicineSapporo 0608638HokkaidoJapan Institute for Chemical Reaction Design and Discovery(WPI-ICReDD) Hokkaido UniversitySapporo 001-0021HokkaidoJapan

BACKGROUND Phlegmonous gastritis(PG)is a rare bacterial infectious disease characterized by neutrophil-based purulent inflammation of the gastric *** most representative causative bacterium is Streptococcus pyogenes,followed by Staphylococcus,Pneumococcus and *** portal venous gas(HPVG)is considered a potentially fatal condition and is rarely associated with *** SUMMARY The white blood cell count of a 70-year-old woman with acute lymphocytic leukemia in complete remission dropped to 100/μL after consolidation *** vital signs were consistent with septic *** blood culture revealed the presence of Bacillus *** computed tomography(CT)and esophagogastroduodenoscopy(EGD)showed marked thickening of the gastric *** with the other findings,CT was suggestive of HPVG,and EGD showed pseudomembrane-like tissue covering the superficial *** examination of gastric biopsy specimens showed mostly necrotic tissue with lymphocytes rather than *** of gastric specimens revealed the presence of Bacillus *** finally diagnosed this case as PG with Bacillus cereus-induced sepsis and *** patient recovered successfully with conservative treatment,chiefly by using carbapenem *** The histopathological finding of this gastric biopsy specimen should be called"neutropenic necrotizing gastritis".

关键词： Phlegmonous gastritis Chemotherapy neutropenia Bacillus cereus Histopathology Case report