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Toyoda Masashi

    Vascular Medicine　Vice-director
Last Updated :2025/04/04

Researcher Information

URL

J-Global ID

Research Interests

  • developmental biology   stem cell biology   cell biology   glycobiology   vascular biology   

Research Areas

  • Life sciences / Human pathology
  • Life sciences / Pathobiochemistry

Published Papers

MISC

Research Grants & Projects

  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2023/04 -2027/03 
    Author : 安樂 真樹; 磯山 隆; 藤原 正親; 小野 稔; 豊田 雅士
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2021/07 -2023/03 
    Author : 豊田 雅士; 松田 明生
     
    不定愁訴（明らかな身体的原因が認められないにも関わらず、頭痛・動悸・疲労感など多岐にわたる自覚症状をもつ状態）がどのような機序で起こるかは未だ不明である。近年SARS-CoV-2感染に伴う後遺症（Long COVID）やワクチン接種に伴う後遺症に不定愁訴に類似した症状が認められる実態が明らかになりつつある。このことは、後遺症のさまざまな症状がウイルス感染等による血管・組織へのダメージが起因となって起こっていることを示唆しており、不定愁訴の分子機序解明への糸口となると考えられる。 そこで本課題では、不定愁訴は血管機能の一時的もしくは慢性的な低下状態によって引き起こされていると考え、その分子機序を探求している。本年度は、in vivoでは組織機能に影響する血管ダメージとはどういった変化がもたらされているかを、ウイルス感染などの重症化リスクの１つである「加齢」を指標として調べた。その結果、血管構造の乱れとともに、その周辺の細胞構造の変化が認められた。血管の変化が周辺細胞の機能へ影響を及ぼしていることが示唆され、その詳細を明らかにすべく検討を進めている。 また本課題では、血管ダメージによって不定愁訴が起こることを前提として、創薬に向けた検討を行っている。血管炎を抑制するスクリーニングによって得られた複数の物質による血管ダメージが引き起こす炎症抑制効果の濃度依存性や、内皮細胞の炎症による細胞内代謝変化が抑制されていることが確認できた。細胞レベルでの効果をさらに個体レベルで検証すべく準備を進めている。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2015/04 -2020/03 
    Author : Umezawa Akihiro
     
    Machine learning analysis was performed on the histopathological image of the teratoma. The critical epigenome of pluripotent stem cells was identified. We analyzed the process of teratoma formation, the interaction between cells, and the site of transplantation. We also clarified the process of forming a teratoma. We attempted to elucidate the structure of teratomas caused by pluripotent stem cells. System pathology is characterized by the elucidation of the mechanisms and principles of cells, organs, and multicellular bodies. It has become possible to elucidate the mechanism of cells and genes that are difficult with conventional methods
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2017/03 
    Author : CHIBA Yumi; SASAKI Norihiko; ITAKURA Yoko; NAKASHIMA Rie
     
    Heart diseases in the elderly are at the top of the cause of death, and treatment options are limited by severity. One means to solve this problem can be said to establish a treatment method by myocardial regeneration by stem cell transplantation. In this study, the aim is to lead appropriateness of the safety and effectiveness of stem cell transplantation in human heart disease pathology by making and evaluating disease model animals to solve this task. Until now, myocardial infarction occurred in young and old mice, and almost completed the evaluation system of heart functions based on ultrasonic evaluation and so on. On the other hand, with regard to the establishment and culture of stem cells as a source of stem cell transplantation to the site of myocardial infarction, both isolation and culture started smoothly, and they are progressing without problems. In the future we will continue to transplant to a disease model.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2013/04 -2016/03 
    Author : Toyoda Masashi; SASAKI Norihiko; ITAKURA Yoko
     
    The cell surface is covered with various glycans, which play a crucial role in biological function. The cell surface dynamics changes of glyccans regulate cellular function during development, differentiation and survival. We investigated glycan changes of the cellular senescence process on human fibroblast, vascular endothelial cells and mesenchymal stem cells with cellular senescence process and/or human aging. The glycan profile of cell surface glycoprotein on cellular senescence process and/or human aging had been significantly changed in fibroblast and mesenchymal stem cells. Thus it was easy to speculate that cellular senescence process was concerned with the change of glycan component of cell surface. Also, we reveal that ganglioside GM1 increase on cell surface vascular endothelial cells accompanying with cellular senescence process and human aging, and that the increased GM1 cause a state of insulin resistance in senescent vascular endothelial cells.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2012/04 -2016/03 
    Author : Hamazaki Takashi; SHINTAKU Haruo; UMEZAWA Akihiro; TOYODA Masashi
     
    Childhood neurotransmitter diseases are genetic syndromes caused by dysfunctional synapsis. Based on our national survey for these diseases, clinical phenotype and laboratory profiles have been illustrated. Conventional laboratory testing for blood and cerebrospinal fluid, however, could not explain pathogenesis of neurological symptoms. Because each of the disease is extremely rare, there is no systematic approach to develop novel treatment. Here we aimed to establish model system by using patient derived iPSCs to elucidate molecular mechanisms for this devastating neurological phenotypes. As the results, we were able to established disease-specific iPSCs and successfully differentiated into neurons. Furthermore, we examined pathogenesis of the disease at cellular and molecular level.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2010/04 -2015/03 
    Author : UMEZAWA Akihiro; KURODA Masahiko; TOYODA Masashi
     
    We examined mesenchymal cells with an extended life span to investigate cardiomyogenic factors comprehensively. Among the mesenchymal cells, we focused on CD29-high CD34-low c-kit-positive CD140a-positive cells, and established a method to select cells capable of differentiating into cardiomyocytes in a high frequency. We implanted mesenchymal cells derived from a series of tissues including placenta into injured hearts. We herewith report to generate an experimental design to obtain proof of concept in a pre-clinical setting for cell-based therapy using tissue-derived mesenchymal cells to injured hearts.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2009/04 -2014/03 
    Author : AKUTSU Hidenori; HAMATANI Toshio; TOYODA Masashi
     
    We analyzed embryonic stem (ES) cells derived from aging mice model. It was found that some genes of Wnt-beta-Catenin signaling were relatively lower expression compared with control ES cells. Then, we successfully derived ES-like cells from beta-Catenin defected embryos. The ES cells showed severely impaired in pluripotential differentiation under loss of Beta-Catenin, although can maintain self-renewal ability. Additionally, we found mixed germ cell tumor was generated from the beta-Catenin defected cells in vivo. Taken together, beta-Catenin functions pleiotropically in differentiation and tumorigenesis in mouse embryo derived stem cells.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2010 -2012 
    Author : AKUTSU Hidenori; TOYODA Masashi
     
    Nuclear reprogramming means that either functional or molecular changes to cells undergoing fate changes, and the mechanism elucidation would deliver great advance not only for the basics of biological systems also more applicable field such as medicine and drug development. In this study, mouse zygotes are focused to be elucidated reprogramming. In early stage of the mammalian preimplantation development, most dramatic epigenetic change is observed the pronuclear formation through their fusion process. Female and male pronuclear materials were collected by micromanipulation technique and were done by the global transcriptional expression analysis using linear amplified RNAs. Gene cluster analysis in conjunction with reprogramming in silico was performed. It was able to extract a convincing gene mainly on a gene in conjunction with the chromatin reprogramming.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2010 -2012 
    Author : HIDA Naoko; UMEZAWA Akihiro; TOYODA Masashi
     
    It has been noted that human mesenchymal stem cells are one of the most suitable cell sources. Mesenchymal stem cells exist in many tissues and differ in their property. In this study, we optimized the cultivation system for clinical purpose. We will improve efficacies of the cell products through information sharing.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2010 -2012 
    Author : TOYODA Masashi; UMEZAWA Akihiro; GOJO Satoshi; ITAKURA Yoko; KAMI Daisuke; MIYOSHI Shunichiro; HIDA Naoko; INOUE Mayu
     
    Amniotic membrane contains a multipotential stem cell population. To explore the clinical application of transplantation of allogeneic amniotic membrane stem cells (AMSCs), we transplanted them into porcine hearts affected by chronic myocardial ischemia as a preclinical study. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2009 -2011 
    Author : KAWAKITA Atsuo; UMEZAWA Akihiro; TOYAMA Yoshiaki; KATO Tatsuo; TOYODA Masashi
     
    Cytokines have been shown to promote regeneration in tissues. In addition, scaffold is required to maintain tissue organization and keep cytokines at target sites. In this study, we generated biodegradable hybrid sheets(poly-DL-lactic-co-glycolic acid(PLGA) sheets) with collagen microsponges. PLGA skeleton facilitates the formation of the hybrid sheets into desired shapes, and the collagen microsponges promote adhesion of the chimeric protein that is composed of cytokines and collagen binding domain of fibronectin. The chimeric protein clearly functioned in vivo, implying that PLGA sheets with chimeric cytokines show promise for use as a tool for the development of therapeutic applications.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2009 -2011 
    Author : UMEZAWA Akihiro; FUJIMOTO Junichiro; HATA Junichi; TOYODA Masashi
     
    Human embryonic stem(ES) cells are difficult to be cultivated in vitro, compared with murine ES cells. In contrast, human embryonal carcinoma(EC) cells can easily be cultivated, compared with human ES cells. In this study, we evaluated human EC cell lines to investigate which human cells can be used as feeder cells. We set specification of human feeder cells in terms of maintenance of human ES cells and preservation of pluripotency. We determined human cell types that are capable of being feeder cells and indeed established human feeder cells.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2007 -2009 
    Author : TOYODA Masashi; HATA Junichi; UMEZAWA Akihiro
     
    The molecular mechanism of maturation of ovum is not clear. For validation of mammalian egg maturation processes during development and aging, we investigated the cell surface carbohydrate expression patterns of ovum and ovary using carbohydrate specific antibodies and lectins. As a result, we showed that some specific carbohydrate structures had important roles for development and aging processes of ovum.

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