Matsubara, Yumiko



School of Medicine, Clinical and Translational Research Center (Shinanomachi)


Project Associate Professor (Non-tenured)

External Links


Research Areas 【 Display / hide

  • Life Science / Hematology and medical oncology

Research Keywords 【 Display / hide

  • Megakaryocytes, Platelets

Research Themes 【 Display / hide

  • Study on a mechanism of megakaryopoiesis and thrombopoiesis, 



Papers 【 Display / hide

  • Adipose-Derived Mesenchymal Stromal/Stem Cell Line Prevents Hepatic Ischemia/Reperfusion Injury in Rats by Inhibiting Inflammasome Activation

    Chen K., Obara H., Matsubara Y., Fukuda K., Yagi H., Ono-Uruga Y., Matsubara K., Kitagawa Y.

    Cell Transplantation (Cell Transplantation)  31 2022.04

    ISSN  09636897

     View Summary

    Mesenchymal stromal/stem cells (MSCs) have shown potential in the treatment of degenerative diseases, including ischemia/reperfusion injury (IRI), which occurs during organ transplantation and represents the main cause of post-transplant graft dysfunction. However, MSCs have heterogeneous characteristics, and studies of MSCs therapy have shown a variety of outcomes. To establish a new effective MSCs therapy, we developed an adipose-derived mesenchymal stromal/stem cell line (ASCL) and compared its therapeutic effects on primary adipose-derived MSCs (ASCs) using a hepatocyte co-culture model of hypoxia/reoxygenation in vitro and a rat model of hepatic IRI in vivo. The results showed that both ASCL and ASCs protect against hypoxia by improving hepatocyte viability, inhibiting reactive oxygen species release, and upregulating transforming growth factor-β in vitro. In vivo, ASCL or ASCs were infused into the spleen 24 h before the induction of rat hepatic IRI. The results showed that ASCL significantly improved the survival outcomes compared with the control (normal saline infusion) with the significantly decreased serum levels of liver enzymes and less damage to liver tissues compared with ASCs. Both ASCL and ASCs suppressed NOD-like receptor family pyrin domain-containing 3 inflammasome activation and subsequently reduced the release of activated IL-1β and IL-18, which is considered an important mechanism underlying ASCL and ASCs infusion in hepatic IRI. In addition, ASCL can promote the release of interleukin-1 receptor antagonist, which was previously reported as a key factor in hampering the inflammatory cascade during hepatic IRI. Our results suggest ASCL as a new candidate for hepatic IRI treatment due to its relatively homogeneous characteristics.

  • Platelet production using adipose-derived mesenchymal stem cells: Mechanistic studies and clinical application

    Ono-Uruga Y., Ikeda Y., Matsubara Y.

    Journal of Thrombosis and Haemostasis (Journal of Thrombosis and Haemostasis)  19 ( 2 ) 342 - 350 2021.02

    ISSN  15387933

     View Summary

    Megakaryocytes (MKs) are platelet progenitor stem cells found in the bone marrow. Platelets obtained from blood draws can be used for therapeutic applications, especially platelet transfusion. The needs for platelet transfusions for clinical situation is increasing, due in part to the growing number of patients undergoing chemotherapy. Platelets obtained from donors, however, have the disadvantages of a limited storage lifespan and the risk of donor-related infection. Extensive effort has therefore been directed at manufacturing platelets ex vivo. Here, we review ex vivo technologies for MK development, focusing on human adipose tissue-derived mesenchymal stem/stromal cell line (ASCL)-based strategies and their potential clinical application. Bone marrow and adipose tissues contain mesenchymal stem/stromal cells that have an ability to differentiate into MKs, which release platelets. Taking advantage of this mechanism, we developed a donor-independent system for manufacturing platelets for clinical application using ASCL established from adipose-derived mesenchymal stem/stromal cells (ASCs). Culture of ASCs with endogenous thrombopoietin and its receptor c-MPL, and endogenous genes such as p45NF-E2 leads to MK differentiation and subsequent platelet production. ASCs compose heterogeneous cells, however, and are not suitable for clinical application. Thus, we established ASCLs, which expand into a more homogeneous population, and fulfill the criteria for mesenchymal stem cells set by the International Society for Cellular Therapy. Using our ASCL culture system with MK lineage induction medium without recombinant thrombopoietin led to peak production of platelets within 12 days, which may be sufficient for clinical application.

  • Megakaryocytes and platelets from a novel human adipose tissue–derived mesenchymal stem cell line

    Tozawa K., Ono-Uruga Y., Yazawa M., Mori T., Murata M., Okamoto S., Ikeda Y., Matsubara Y.

    Blood (Blood)  133 ( 7 ) 633 - 643 2019.02

    ISSN  00064971

     View Summary

    The clinical need for platelet transfusions is increasing; however, donor-dependent platelet transfusions are associated with practical problems, such as the limited supply and the risk of infection. Thus, we developed a manufacturing system for platelets from a donor-independent cell source: a human adipose-derived mesenchymal stromal/stem cell line (ASCL). The ASCL was obtained using an upside-down culture flask method and satisfied the minimal criteria for defining mesenchymal stem cells (MSCs) by The International Society for Cellular Therapy. The ASCL showed its proliferation capacity for ‡2 months without any abnormal karyotypes. The ASCL was cultured in megakaryocyte induction media. ASCL-derived megakaryocytes were obtained, with a peak at day 8 of culture, and ASCL-derived platelets (ASCL-PLTs) were obtained, with a peak at day 12 of culture. We observed that CD42b1 cells expressed an MSC marker (CD90) which is related to cell adhesion. Compared with peripheral platelets, ASCL-PLTs exhibit higher levels of PAC1 binding, P-selectin surface exposure, ristocetin-induced platelet aggregation, and ADP-induced platelet aggregation, as well as similar levels of fibrinogen binding and collagen-induced platelet aggregation. ASCL-PLTs have lower epinephrine-induced platelet aggregation. The pattern of in vivo kinetics after infusion into irradiated immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/ SzJ mice was similar to that of platelet concentrates. ASCL-PLTs have similar characteristics to those of peripheral platelets and might have an additional function as MSCs. The establishment of the ASCL and its differentiation into ASCL-PLTs do not require gene transfer, and endogenous thrombopoietin is used for differentiation. The present protocol is a simple method that does not require feeder cells, further enhancing the clinical application of our approach.

  • Identification of ADRA2A polymorphisms related to shear-mediated platelet function.

    Yabe Mariko, Matsubara Yumiko, Takahashi Shinichi, Ishihara Hiroaki, Shibano Toshiro, Miyaki Koichi, Omae Kazuyuki, Watanabe Gentaro, Murata Mitsuru, Ikeda Yasuo

    Biochemical and Biophysical Research Communications 347 ( 4 ) 1001-1005 2006.09

    Research paper (scientific journal), Joint Work

  • 学会聴講記 第47回米国血液学会(ASH)

    松原 由美子

    International Review of Thrombosis 1 ( 2 ) 128-131 2006.07

    Research paper (scientific journal), Single Work

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

Presentations 【 Display / hide

  • Human Pre-adipocytes Differentiate into Megakaryocytes and Platelets using Endogenous Thrombopoietin


    XXIV The International Society on Thrombosis and Haemostasis, 


  • von Willebrand因子との反応性に関与するGPIbαの遺伝子多型

    松原 由美子, 村田 満, 林 朋博, 鈴木 啓二郎, 岡村 陽介, 半田 誠, 石原 宏明,芝野 俊郎, 池田 康夫

    第27回日本血栓止血学会学術集会 (奈良) , 


    Oral presentation (general)

  • Platelet glycoprotein Ib alpha polymorphisms affect the interaction with von Willebrand factor under flow conditions.

    Matsubara Yumiko, Murata Mitsuru, Hayashi Tomohiro, Suzuki Keijiro, Okamura Yosuke, Handa Makoto, Ishihara Hiroaki, Shibano Toshiro, Ikeda Yasuo

    UK-Japan Platelet Conference (UK) , 


    Oral presentation (general)

  • Polymorphisms of platelet glycoprotein Ib_ affect its interaction with von Willbrand factor under flow conditions.

    Matsubara Yumiko, Murata Mitsuru, Hayashi T, Ikeda Yasuo

    Annual Meeting and Exposition, The American Society of Hematology (San Diego, USA) , 


    Poster presentation

  • ADAMTS13 (von Willebrand factor-cleaving protease) is expressed in human platelets.

    Suzuki Misako, Murata Mitsuru, Matsubara Yumiko, Yokoyama Kenji, Ambo Hironobu, Uchida Toshihiro, Ishihara Hiroaki, Shibano Toshiro, Okada Y, Ikeda Yasuo

    Annual Meeting and Exposition, The American Society of Hematology (San Diego, USA) , 


    Poster presentation

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

  • 血小板創製技術の医療応用


    国立研究開発法人日本医療研究開発機構, Principal investigator

  • 皮下脂肪幹細胞から単離されるプレ巨核球前駆細胞からの血小板産生におけるc-MPLの役割


    公益財団法人 先進医薬研究振興財団, 血液医学分野 一般研究助成, Principal investigator

  • 革新的血小板創製技術の確立と医療応用


    公益財団法人 神奈川科学技術アカデミー, Principal investigator

  • 経口血小板増多剤による肝硬変に対する新規肝再生


    日本学術振興会, Grant-in-Aid for Scientific Research, Coinvestigator(s)

  • 脂肪幹細胞からのプレ巨核球前駆細胞の同定と特性の解析


    日本学術振興会, Grant-in-Aid for Scientific Research, Principal investigator

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