谷 英典 (タニ ヒデノリ)

Tani, Hidenori

写真a

所属(所属キャンパス)

医学部 心臓病未来治療学共同研究講座 (信濃町)

職名

特任助教(有期)

 

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  • Cardiac reprogramming reduces inflammatory macrophages and improves cardiac function in chronic myocardial infarction.

    Abe Y, Tani H, Sadahiro T, Yamada Y, Akiyama T, Nakano K, Honda S, Ko S, Anzai A, Ieda M

    Biochemical and biophysical research communications (Biochemical and Biophysical Research Communications)  690   149272 2023年11月

    ISSN  0006-291X

     概要を見る

    Cardiomyocytes (CMs) have little regenerative capacity. After myocardial infarction (MI), scar formation and myocardial remodeling proceed in the infarct and non-infarct areas, respectively, leading to heart failure (HF). Prolonged activation of cardiac fibroblasts (CFs) and inflammatory cells may contribute to this process; however, therapies targeting these cell types remain lacking. Cardiac reprogramming converts CFs into induced CMs, reduces fibrosis, and improves cardiac function in chronic MI through the overexpression of Mef2c/Gata4/Tbx5/Hand2 (MGTH). However, whether cardiac reprogramming reduces inflammation in infarcted hearts remains unclear. Moreover, the mechanism through which MGTH overexpression in CFs affects inflammatory cells remains unknown. Here, we showed that inflammation persists in the myocardium until three months after MI, which can be reversed with cardiac reprogramming. Single-cell RNA sequencing demonstrated that CFs expressed pro-inflammatory genes and exhibited strong intercellular communication with inflammatory cells, including macrophages, in chronic MI. Cardiac reprogramming suppressed the inflammatory profiles of CFs and reduced the relative ratios and pro-inflammatory signatures of cardiac macrophages. Moreover, fluorescence-activated cell sorting analysis (FACS) revealed that cardiac reprogramming reduced the number of chemokine receptor type 2 (CCR2)-positive inflammatory macrophages in the non-infarct areas in chronic MI, thereby restoring myocardial remodeling. Thus, cardiac reprogramming reduced the number of inflammatory macrophages to exacerbate cardiac function after MI.

  • Seamless and non-destructive monitoring of extracellular microRNAs during cardiac differentiation from human pluripotent stem cells

    Sekine O., Kanaami S., Masumoto K., Aihara Y., Morita-Umei Y., Tani H., Soma Y., Umei T.C., Haga K., Moriwaki T., Kawai Y., Ohno M., Kishino Y., Kanazawa H., Fukuda K., Ieda M., Tohyama S.

    Stem Cell Reports (Stem Cell Reports)  18 ( 10 ) 1925 - 1939 2023年10月

    ISSN  22136711

     概要を見る

    Monitoring cardiac differentiation and maturation from human pluripotent stem cells (hPSCs) and detecting residual undifferentiated hPSCs are indispensable for the development of cardiac regenerative therapy. MicroRNA (miRNA) is secreted from cells into the extracellular space, and its role as a biomarker is attracting attention. Here, we performed an miRNA array analysis of supernatants during the process of cardiac differentiation and maturation from hPSCs. We demonstrated that the quantification of extracellular miR-489-3p and miR-1/133a-3p levels enabled the monitoring of mesoderm and cardiac differentiation, respectively, even in clinical-grade mass culture systems. Moreover, extracellular let-7c-5p levels showed the greatest increase with cardiac maturation during long-term culture. We also verified that residual undifferentiated hPSCs in hPSC-derived cardiomyocytes (hPSC-CMs) were detectable by measuring miR-302b-3p expression, with a detection sensitivity of 0.01%. Collectively, we demonstrate that our method of seamlessly monitoring specific miRNAs secreted into the supernatant is non-destructive and effective for the quality evaluation of hPSC-CMs.

  • Heart-derived collagen promotes maturation of engineered heart tissue

    Tani H., Kobayashi E., Yagi S., Tanaka K., Kameda-Haga K., Shibata S., Moritoki N., Takatsuna K., Moriwaki T., Sekine O., Umei T.C., Morita Y., Soma Y., Kishino Y., Kanazawa H., Fujita J., Hattori S., Fukuda K., Tohyama S.

    Biomaterials (Biomaterials)  299   122174 2023年08月

    ISSN  01429612

     概要を見る

    Although the extracellular matrix (ECM) plays essential roles in heart tissue engineering, the optimal ECM components for heart tissue organization have not previously been elucidated. Here, we focused on the main ECM component, fibrillar collagen, and analyzed the effects of collagens on heart tissue engineering, by comparing the use of porcine heart-derived collagen and other organ-derived collagens in generating engineered heart tissue (EHT). We demonstrate that heart-derived collagen induces better contraction and relaxation of human induced pluripotent stem cell-derived EHT (hiPSC-EHT) and that hiPSC-EHT with heart-derived collagen exhibit more mature profiles than those with collagens from other organs. Further, we found that collagen fibril formation and gel stiffness influence the contraction, relaxation, and maturation of hiPSC-EHT, suggesting the importance of collagen types III and type V, which are relatively abundant in the heart. Thus, we demonstrate the effectiveness of organ-specific collagens in tissue engineering and drug discovery.

  • Response by Sadahiro et al to Letter Regarding Article, "Direct Reprogramming Improves Cardiac Function and Reverses Fibrosis in Chronic Myocardial Infarction".

    Sadahiro T, Tani H, Ieda M

    Circulation 148 ( 2 ) 172 - 173 2023年07月

    ISSN  0009-7322

  • Cardiac Regenerative Therapy Using Human Pluripotent Stem Cells for Heart Failure: A State-of-the-Art Review

    KISHINO Y., TOHYAMA S., MORITA Y., SOMA Y., TANI H., OKADA M., KANAZAWA H., FUKUDA K.

    Journal of Cardiac Failure (Journal of Cardiac Failure)  29 ( 4 ) 503 - 513 2023年04月

    ISSN  10719164

     概要を見る

    Heart transplantation (HT) is the only definitive treatment available for patients with end-stage heart failure who are refractory to medical and device therapies. However, HT as a therapeutic option, is limited by a significant shortage of donors. To overcome this shortage, regenerative medicine using human pluripotent stem cells (hPSCs), such as human embryonic stem cells and human-induced pluripotent stem cells (hiPSCs), has been considered an alternative to HT. Several issues, including the methods of large-scale culture and production of hPSCs and cardiomyocytes, the prevention of tumorigenesis secondary to contamination of undifferentiated stem cells and non-cardiomyocytes, and the establishment of an effective transplantation strategy in large-animal models, need to be addressed to fulfill this unmet need. Although post-transplantation arrhythmia and immune rejection remain problems, the ongoing rapid technological advances in hPSC research have been directed toward the clinical application of this technology. Cell therapy using hPSC-derived cardiomyocytes is expected to serve as an integral component of realistic medicine in the near future and is being potentially viewed as a treatment that would revolutionize the management of patients with severe heart failure.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

総説・解説等 【 表示 / 非表示

  • Seamless and Non-Destructive Monitoring of Extracellular MicroRNAs during Cardiac Differentiation and Maturation from Human Pluripotent Stem Cells(タイトル和訳中)

    関根 乙矢, 遠山 周吾, 金編 さやか, 梅井 唯加, 谷 英典, 相馬 雄輔, 梅井 智彦, 芳賀 康太郎, 森脇 大順, 大野 昌利, 岸野 喜一, 金澤 英明, 福田 恵一, 家田 真樹

    日本心臓病学会学術集会抄録 ((一社)日本心臓病学会)  71回   YIA - 4 2023年09月

  • 心臓コラーゲンを用いた成熟化ヒト心筋組織の開発と創薬研究,疾患モデルへの応用

    谷 英典

    心臓 ((公財)日本心臓財団)  54 ( 12 ) 1408 - 1408 2022年12月

    ISSN  0586-4488

  • Translational Cardiology 基礎から臨床へ iPS心筋を用いた創薬研究

    谷 英典, 遠山 周吾

    心臓 ((公財)日本心臓財団)  54 ( 1 ) 36 - 42 2022年01月

    ISSN  0586-4488

競争的研究費の研究課題 【 表示 / 非表示

  • ヒトiPS細胞由来三次元心筋組織を用いた心不全の新規病態解明と治療法の開発

    2023年04月
    -
    2026年03月

    科学研究費助成事業, 谷 英典, 若手研究, 未設定

     研究概要を見る

    HFpEFの病態は、高血圧や糖尿病、脂質異常症といった併存症により、全身性に酸化ストレスや炎症が惹起された結果、血管内皮の障害が起き、eNOS が関与するシグナル伝達経路 (eNOS-NO-cGMP-PKG 経路) が障害され、左室の拡張障害が生じることであるというのが近年の動物実験で明らかになってきた。ヒトの細胞、組織においてはHFpEFのモデルは確立しておらず、機序の解明や治療薬の開発も急務となっている。本研究の概要は、「HFpEFにおける心筋拡張障害はヒト心筋組織のどういった変化によって引き起こされるのか」であり、心臓病領域の研究における重要な研究課題を担っている。