Kishino, Yoshikazu

写真a

Affiliation

School of Medicine, Endowed Course for Severe Heart Failure Treatment (Shinanomachi)

Position

Project Assistant Professor (Non-tenured)/Project Research Associate (Non-tenured)/Project Instructor (Non-tenured)

 

Research Areas 【 Display / hide

  • Cardiovascular medicine

Research Keywords 【 Display / hide

  • cardiac regeneration

Research Themes 【 Display / hide

  • cardiac regeneration therapy using iPS cells, 

    2012.04
    -
    Present

 

Books 【 Display / hide

  • 循環器内科

    KISHINO Yoshikazu, 科学評論社, 2015

    Scope: 4. 特集 心不全の最近の話題 話題:心筋再生医療の現状と展望

  • 動物細胞の培養を成功させる条件設定集

    KISHINO Yoshikazu, 技術情報協会, 2014

    Scope: 第2章 細胞死・細胞凝集・増殖不良・不安定化を防ぐ培養の成功させる条件設定,第8節iPS・幹細胞の培養を成功させる技術 心筋組織の培養と条件の設定

  • stem cell research and regeneration medicine

    KISHINO Yoshikazu, nanzandou, 2013

    Scope: chapter 20 cardiac regeneration

  • 救急・ERノート

    KISHINO Yoshikazu, 羊土社, 2012.11

    Scope: 原因疾患へのアプローチ 7 ERでの感染性心内膜炎

Papers 【 Display / hide

  • Concise Review: Genetic and Epigenetic Regulation of Cardiac Differentiation from Human Pluripotent Stem Cells

    Fujita J., Tohyama S., Kishino Y., Okada M., Morita Y.

    Stem Cells (Stem Cells)  37 ( 8 ) 992 - 1002 2019.08

    ISSN  10665099

     View Summary

    © AlphaMed Press 2019 Human pluripotent stem cells (hPSCs), including both embryonic stem cells and induced pluripotent stem cells, are the ideal cell sources for disease modeling, drug discovery, and regenerative medicine. In particular, regenerative therapy with hPSC-derived cardiomyocytes (CMs) is an unmet medical need for the treatment of severe heart failure. Cardiac differentiation protocols from hPSCs are made on the basis of cardiac development in vivo. However, current protocols have yet to yield 100% pure CMs, and their maturity is low. Cardiac development is regulated by the cardiac gene network, including transcription factors (TFs). According to our current understanding of cardiac development, cardiac TFs are sequentially expressed during cardiac commitment in hPSCs. Expression levels of each gene are strictly regulated by epigenetic modifications. DNA methylation, histone modification, and noncoding RNAs significantly influence cardiac differentiation. These complex circuits of genetic and epigenetic factors dynamically affect protein expression and metabolic changes in cardiac differentiation and maturation. Here, we review cardiac differentiation protocols and their molecular machinery, closing with a discussion of the future challenges for producing hPSC-derived CMs. Stem Cells 2019;37:992–1002.

  • Selective elimination of undifferentiated human pluripotent stem cells using pluripotent state-specific immunogenic antigen Glypican-3

    Okada M., Tada Y., Seki T., Tohyama S., Fujita J., Suzuki T., Shimomura M., Ofuji K., Kishino Y., Nakajima K., Tanosaki S., Someya S., Kanazawa H., Senju S., Nakatsura T., Fukuda K.

    Biochemical and Biophysical Research Communications (Biochemical and Biophysical Research Communications)  511 ( 3 ) 711 - 717 2019.04

    ISSN  0006291X

     View Summary

    © 2019 Elsevier Inc. Immunogenicity of immature pluripotent stem cells is a topic of intense debate. Immunogenic antigens, which are specific in pluripotent states, have not been described previously. In this study, we identified glypican-3 (GPC3), a known carcinoembryonic antigen, as a pluripotent state-specific immunogenic antigen. Additionally, we validated the applicability of human leukocyte antigen (HLA)-class I-restricted GPC3-reactive cytotoxic T lymphocytes (CTLs) in the removal of undifferentiated pluripotent stem cells (PSCs) from human induced pluripotent stem cell (hiPSC)-derivatives. HiPSCs uniquely express GPC3 in pluripotent states and were rejected by GPC3-reactive CTLs, which were sensitized with HLA-class I-restricted GPC3 peptides. Furthermore, GPC3-reactive CTLs selectively removed undifferentiated PSCs from hiPSC-derivatives in vitro and inhibited tumor formation in vivo. Our results demonstrate that GPC3 works as a pluripotent state-specific immunogenic antigen in hiPSCs and is applicable to regenerative medicine as a method of removing undifferentiated PSCs, which are the main cause of tumor formation.

  • Development of a transplant injection device for optimal distribution and retention of human induced pluripotent stem cell‒derived cardiomyocytes

    Tabei R., Kawaguchi S., Kanazawa H., Tohyama S., Hirano A., Handa N., Hishikawa S., Teratani T., Kunita S., Fukuda J., Mugishima Y., Suzuki T., Nakajima K., Seki T., Kishino Y., Okada M., Yamazaki M., Okamoto K., Shimizu H., Kobayashi E., Tabata Y., Fujita J., Fukuda K.

    Journal of Heart and Lung Transplantation (Journal of Heart and Lung Transplantation)  38 ( 2 ) 203 - 214 2019.02

    ISSN  10532498

     View Summary

    © 2018 Elsevier Ltd BACKGROUND: Induced pluripotent stem cell (iPSC)‒based regenerative therapy is a promising strategy for cardiovascular disease treatment; however, the method is limited by the myocardial retention of grafted iPSCs. Thus, an injection protocol that efficiently introduces and retains human iPSC-derived cardiomyocytes (hiPSC-CMs) within the myocardium is urgently needed. The objective of the present study was to develop a method to improve the retention of hiPSCs in the myocardium for cardiac therapy. METHODS: We efficiently produced hiPSC-CM spheroids in 3-dimensional (3D) culture using microwell plates, and developed an injection device for optimal 3D distribution of the spheroids in the myocardial layer. Device biocompatibility was assessed with purified hiPSC-CM spheroids. Device effectiveness was evaluated in 10- to 15-month-old farm pigs (n = 15) and 5- to 24-month-old micro-minipigs (n = 20). The pigs were euthanized after injection, and tissues were harvested for retention and histologic analysis. RESULTS: We demonstrated an injection device for direct intramyocardial transplantation of hiPSC-CM spheroids from large-scale culture. The device had no detrimental effects on cell viability, spheroid shape, or size. Direct epicardial injection of spheroids mixed with gelatin hydrogel into beating porcine hearts using this device resulted in better distribution and retention of transplanted spheroids in a layer within the myocardium than did conventional needle injection procedures. CONCLUSIONS: The combination of the newly developed transplant device and spheroid formation promotes the retention of transplanted CMs. These findings support the clinical application of hiPSC-CM spheroid‒based cardiac regenerative therapy in patients with heart failure.

  • Automated Deep Learning-Based System to Identify Endothelial Cells Derived from Induced Pluripotent Stem Cells

    Kusumoto D., Lachmann M., Kunihiro T., Yuasa S., Kishino Y., Kimura M., Katsuki T., Itoh S., Seki T., Fukuda K.

    Stem Cell Reports (Stem Cell Reports)  10 ( 6 ) 1687 - 1695 2018.06

    ISSN  22136711

     View Summary

    © 2018 The Author(s) Deep learning technology is rapidly advancing and is now used to solve complex problems. Here, we used deep learning in convolutional neural networks to establish an automated method to identify endothelial cells derived from induced pluripotent stem cells (iPSCs), without the need for immunostaining or lineage tracing. Networks were trained to predict whether phase-contrast images contain endothelial cells based on morphology only. Predictions were validated by comparison to immunofluorescence staining for CD31, a marker of endothelial cells. Method parameters were then automatically and iteratively optimized to increase prediction accuracy. We found that prediction accuracy was correlated with network depth and pixel size of images to be analyzed. Finally, K-fold cross-validation confirmed that optimized convolutional neural networks can identify endothelial cells with high performance, based only on morphology. Kusumoto et al. developed an automated system to identify endothelial cells derived from induced pluripotent stem cells, based only on morphology. Performance, as assessed by F1 score and accuracy, was correlated with network depth and pixel size of training images. K-fold validation confirmed that endothelial cells are identified automatically with high accuracy using only generalized morphological features.

  • Generation of Induced Pluripotent Stem Cells from Human Peripheral T Cells Using Sendai Virus in Feeder-free Conditions.

    KISHINO Yoshikazu

    The Journal of Visualized Experiments  2015

    Research paper (scientific journal), Single Work

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Papers, etc., Registered in KOARA 【 Display / hide

Presentations 【 Display / hide

  • Novel Pathological Detection System of Induced Pluripotent Stem Cell-derived Cardiomyocytes Using T-cell Receptor Gene Locus for Cell Transplantation Therapy

    KISHINO Yoshikazu

    International Society for Stem Cell Research 2016 Annual Meeting, 2016, Poster (general)

  • Novel Pathological Detection System of Induced Pluripotent Stem Cell-derived Cardiomyocytes Using T-cell Receptor Gene Locus for Cell Transplantation Therapy

    KISHINO Yoshikazu

    Keystone Symposia, 2015, Poster (general)

  • The Novel Identifying Method of Transplanted Cells Using T-cell Receptor Gene Locus

    KISHINO Yoshikazu

    第13回日本再生医療学会, 2014, Poster (general)

  • Novel Pathological Detection System of Induced Pluripotent Stem Cell-derived Cardiomyocytes Using T-cell Receptor Gene Locus for Cell Transplantation Therapy

    KISHINO Yoshikazu

    第78回日本循環器学会, 2014, Oral Presentation(general)

  • Novel Pathological Detection System of Induced Pluripotent Stem Cell-derived Cardiomyocytes Using T-cell Receptor Gene Locus for Cell Transplantation Therapy

    KISHINO Yoshikazu

    American Heart Association Scientific Sessions, 2013, Poster (general)

Research Projects of Competitive Funds, etc. 【 Display / hide

  • ヒト多能性幹細胞からの効率的な心筋細胞分化に向けた新規低分子化合物の開発

    2020.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 岸野 喜一, Grant-in-Aid for Early-Career Scientists , Principal Investigator

  • ヒト多能性幹細胞からの効率的な心筋細胞分化に向けた新規低分子化合物の開発

    2018.04
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 岸野 喜一, Grant-in-Aid for Early-Career Scientists , Principal Investigator