Development of single cell analysis technology of tissue stem cells using electrical property

• Project/Area Number: 15K06853
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: MABUCHI Yo 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (50424172)
• Co-Investigator(Kenkyū-buntansha): 赤澤 智宏 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (80291160)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 間葉系幹細胞 / 細胞分離 / 細胞マーカー / 組織幹細胞 / 単一細胞解析 / Single cell 解析 / 電気物性 / 比誘電率

Outline of Final Research Achievements

In this study, we developed a technology to analyze cell properties without labeling such as fluorescent dyes. We established the technology to define the stem cell properties using the electrical properties as the indicator. Electrical property analysis suggested that tissue stem cells have specific electrical properties. Furthermore, the electrical properties were correlated with stemness. This technology is considered to contribute a diagnosis and stem cell therapy in research and medical field.

Academic Significance and Societal Importance of the Research Achievements

物質の電気的性質は、誘電率[Cm]（電気のためやすさ）と導電率[K]（電気の流れやすさ）、細胞径[d]という3つのパラメーターで表される。一般的な細胞の細胞膜はほぼ絶縁体とみなすことができ、電極を通して測定される電気物性は、細胞の形状・性質に依存する。特定の細胞集団を蛍光色素などの標識なしで同定が可能であれば、細胞種・生物種を超えた普遍的な指標としてユニバーサルに利用できると考えられる。この技術を応用し、幹細胞性やがん化などの細胞異常をラベルフリーでモニターすることが可能となれば、研究ならびに医療現場において、細胞診断や幹細胞治療に大きな貢献をもたらすと考えられる。

Research Products

• [Int'l Joint Research] University of Birmingham(United Kingdom)
• [Journal Article] Pericytes as a Source of Osteogenic Cells in Bone Fracture Healing (2019)
  • Author(s): Supakul Sopak、Yao Kenta、Ochi Hiroki、Shimada Tomohito、Hashimoto Kyoko、Sunamura Satoko、Mabuchi Yo、Tanaka Miwa、Akazawa Chihiro、Nakamura Takuro、Okawa Atsushi、Takeda Shu、Sato Shingo
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 5 Pages: 1079-1079
  • DOI: 10.3390/ijms20051079
  • Peer Reviewed / Open Access
• [Journal Article] Construction of Continuous Capillary Networks Stabilized by Pericyte-like Perivascular Cells (2019)
  • Author(s): Kyoko Yamamoto, Kohei Tanimura, Masafumi Watanabe, Hiromu Sano, Hiroyuki Uwamori, Yo Mabuchi, Yumi Matsuzaki, Seok Chung, Roger D. Kamm, Kazuo Tanishita, Ryo Sudo
  • Journal Title: Tissue Engineering Part A Volume: 25 Issue: 5-6 Pages: 499-510
  • DOI: 10.1089/ten.tea.2018.0186
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Generation of orthotopically functional salivary gland from embryonic stem cells (2018)
  • Author(s): Tanaka Junichi、Ogawa Miho、Hojo Hironori、Kawashima Yusuke、Mabuchi Yo、Hata Kenji、Nakamura Shiro、Yasuhara Rika、Takamatsu Koki、Irie Tarou、Fukada Toshiyuki、Sakai Takayoshi、Inoue Tomio、Nishimura Riko、Ohara Osamu、Saito Ichiro、Ohba Shinsuke、Tsuji Takashi、Mishima Kenji
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 4216-4216
  • DOI: 10.1038/s41467-018-06469-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Anterior cruciate ligament-derived mesenchymal stromal cells have a propensity to differentiate into the ligament lineage (2018)
  • Author(s): Ogata Yusuke、Mabuchi Yo、Shinoda Kosuke、Horiike Yuta、Mizuno Mitsuru、Otabe Koji、Suto Eriko Grace、Suzuki Nobuharu、Sekiya Ichiro、Akazawa Chihiro
  • Journal Title: Regenerative Therapy Volume: 8 Pages: 20-28
  • DOI: 10.1016/j.reth.2017.12.001
  • Peer Reviewed / Open Access
• [Journal Article] Specific markers and properties of synovial mesenchymal stem cells in the surface, stromal, and perivascular regions. (2018)
  • Author(s): Mizuno M, Katano H, Mabuchi Y, Ogata Y, Ichinose S, Fujii S, Otabe K, Komori K, Ozeki N, Koga H, Tsuji K, Akazawa C, Muneta T, Sekiya I.
  • Journal Title: Stem Cell Res Ther. Volume: 9 Issue: 1 Pages: 123-123
  • DOI: 10.1186/s13287-018-0870-9
  • Peer Reviewed / Open Access
• [Journal Article] Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A (2018)
  • Author(s): Kyoko Hashimoto, Hiroki Ochi, Satoko Sunamura, Nobuyoshi Kosaka, Yo Mabuchi, Toru Fukuda, Kenta Yao, Hiroaki Kanda, Keisuke Ae, Atsushi Okawa, Chihiro Akazawa, Takahiro Ochiya, Mitsuru Futakuchi, Shu Takeda, Shingo Sato
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. Volume: 115(9) Issue: 9 Pages: 2204-2209
  • DOI: 10.1073/pnas.1717363115
  • Peer Reviewed / Open Access
• [Journal Article] Recapitulation of Extracellular LAMININ Environment Maintains Stemness of Satellite Cells In?Vitro (2018)
  • Author(s): Ishii Kana、Sakurai Hidetoshi、Suzuki Nobuharu、Mabuchi Yo、Sekiya Ichiro、Sekiguchi Kiyotoshi、Akazawa Chihiro
  • Journal Title: Stem Cell Reports Volume: 10 Issue: 2 Pages: 568-582
  • DOI: 10.1016/j.stemcr.2017.12.013
  • NAID: 120006454685
  • Peer Reviewed / Open Access
• [Journal Article] Technical advantage of recombinant collagenase for isolation of muscle stem cells (2017)
  • Author(s): Ishii Kana、Suzuki Nobuharu、Mabuchi Yo、Sekiya Ichiro、Akazawa Chihiro
  • Journal Title: Regenerative Therapy Volume: 7 Pages: 1-7
  • DOI: 10.1016/j.reth.2017.06.001
  • Peer Reviewed / Open Access
• [Journal Article] Isolation of dental pulp stem cells with high osteogenic potential (2017)
  • Author(s): Yasui Takazumi、Mabuchi Yo、Morikawa Satoru、Onizawa Katsuhiro、Akazawa Chihiro、Nakagawa Taneaki、Okano Hideyuki、Matsuzaki Yumi
  • Journal Title: Inflammation and Regeneration Volume: 37 Issue: 1 Pages: 8-8
  • DOI: 10.1186/s41232-017-0039-4
  • Peer Reviewed / Open Access
• [Journal Article] Differentiation of Oligodendrocyte Precursor Cells from Sox10-Venus Mice to Oligodendrocytes and Astrocytes (2017)
  • Author(s): Suzuki Nobuharu、Sekimoto Kaori、Hayashi Chikako、Mabuchi Yo、Nakamura Tetsuya、Akazawa Chihiro
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 14133-14133
  • DOI: 10.1038/s41598-017-14207-0
  • Peer Reviewed / Open Access
• [Journal Article] Prospectively isolated mesenchymal stem/stromal cells are enriched in the CD73+ population and exhibit efficacy after transplantation (2017)
  • Author(s): Suto Eriko Grace、Mabuchi Yo、Suzuki Nobuharu、Suzuki Koji、Ogata Yusuke、Taguchi Miyu、Muneta Takeshi、Sekiya Ichiro、Akazawa Chihiro
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 4838-4838
  • DOI: 10.1038/s41598-017-05099-1
  • Peer Reviewed / Open Access
• [Journal Article] Induction of hair follicle dermal papilla cell properties in human induced pluripotent stem cell-derived multipotent LNGFR(+)THY-1(+) mesenchymal cells (2017)
  • Author(s): Ophelia Veraitch, Yo Mabuchi, Yumi Matsuzaki, Takashi Sasaki, Hironobu Okuno, Aki Tsukashima, Masayuki Amagai, Hideyuki Okano, Manabu Ohyama
  • Journal Title: Scientific Reports Volume: 21 Issue: 1 Pages: 42777-42777
  • DOI: 10.1038/srep42777
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Notch2 signaling regulates the proliferation of murine bone marrow-derived mesenchymal stem/stromal cells via c-Myc expression. (2016)
  • Author(s): Yukio S, Mabuchi Y, Miyamoto K, Araki D, Niibe K, Houlihan DD, Morikawa S, Nakagawa T, Nakajima T, Akazawa C, Hori S, Okano H, Matsuzaki Y
  • Journal Title: PLOS ONE Volume: 11（11） Issue: 11 Pages: 0165946-0165946
  • DOI: 10.1371/journal.pone.0165946
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Growth differentiation factor 6 derived from mesenchymal stem/stromal cells reduces age-related functional deterioration in multiple tissues. (2016)
  • Author(s): Hisamatsu D, Ohno-Oishi M, Nakamura S, Mabuchi Y, Naka-Kaneda H
  • Journal Title: Aging (Albany NY). Volume: 8(6) Issue: 6 Pages: 1259-75
  • DOI: 10.18632/aging.100982
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model. (2016)
  • Author(s): Ogawa Y, Morikawa S, Okano H, Mabuchi Y, Suzuki S, Yaguchi T, Sato Y, Mukai S, Yaguchi S, Inaba T, Okamoto S, Kawakami Y, Tsubota K, Matsuzaki Y, Shimmura S.
  • Journal Title: eLife Volume: 5
  • DOI: 10.7554/elife.09394
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Not single but periodic injections of synovial mesenchymal stem cells maintain viable cells in knees and inhibit osteoarthritis progression in rats. (2016)
  • Author(s): Ozeki N, Muneta T, Koga H, Nakagawa Y, Mizuno M, Tsuji K, Mabuchi Y, Akazawa C, Kobayashi E, Matsumoto K, Futamura K, Saito T, Sekiya I
  • Journal Title: Osteoarthritis Cartilage Volume: in press Issue: 6 Pages: 1061-70
  • DOI: 10.1016/j.joca.2015.12.018
  • NAID: 40021330438
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prospective isolation of resident adult human mesenchymal stem cell population from multiple organs. (2016)
  • Author(s): Mabuchi Y, Matsuzaki Y
  • Journal Title: Int J Hematol. Volume: 103(2) Issue: 2 Pages: 138-44
  • DOI: 10.1007/s12185-015-1921-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Purified Human Dental Pulp Stem Cells Promote Osteogenic Regeneration. (2015)
  • Author(s): Yasui T, Mabuchi Y, Toriumi H, Ebine T, Niibe K, Houlihan DD, Morikawa S, Onizawa K, Kawana H, Akazawa C, Suzuki N, Nakagawa T, Okano H, Matsuzaki Y.
  • Journal Title: journal of Dental Research Volume: 95 Issue: 2 Pages: 206-214
  • DOI: 10.1177/0022034515610748
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Loss of the Homeodomain Transcription Factor Prep1 Perturbs Adult Hematopoiesis in the Bone Marrow. (2015)
  • Author(s): Yoshioka K, Oda A, Notsu C, Ohtsuka T, Kawai Y, Suzuki S, Nakamura T, Mabuchi Y, Matsuzaki Y, Goitsuka R.
  • Journal Title: PLoS One. Volume: 10(8) Issue: 8 Pages: e0136107-e0136107
  • DOI: 10.1371/journal.pone.0136107
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD34 and CD49f Double-Positive and Lineage Marker-Negative Cells Isolated from Human Myometrium Exhibit Stem Cell-Like Properties Involved in Pregnancy-Induced Uterine Remodeling. (2015)
  • Author(s): Ono M, Kajitani T, Uchida H, Arase T, Oda H, Uchida S, Ota K, Nagashima T, Masuda H, Miyazaki K, Asada H, Hida N, Mabuchi Y, Morikawa S, Ito M, Bulun SE, Okano H, Matsuzaki Y, Yoshimura Y, Maruyama T.
  • Journal Title: Biol Reprod. Volume: 93(2)
  • Peer Reviewed / Open Access
• [Journal Article] Purified Human Synovium Mesenchymal Stem Cells as a Good Resource for Cartilage Regeneration. (2015)
  • Author(s): Ogata Y, Mabuchi Y, Yoshida M, Suto EG, Suzuki N, Muneta T, Sekiya I, Akazawa C.
  • Journal Title: PLoS One. Volume: 10(6) Issue: 6 Pages: e0129096-e0129096
  • DOI: 10.1371/journal.pone.0129096
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human somatic stem cell-based therapy for cartilage regeneration. (2015)
  • Author(s): Mabuchi Y, Okano H.
  • Journal Title: Ann Transl Med. Volume: 3(Suppl 1)
  • Peer Reviewed / Open Access
• [Journal Article] Muscle Satellite Cell Protein Teneurin-4 Regulates Differentiation During Muscle Regeneration. (2015)
  • Author(s): Ishii K, Suzuki N, Mabuchi Y, Ito N, Kikura N, Fukada S, Okano H, Takeda S, Akazawa C.
  • Journal Title: Stem Cells. Volume: 33(10) Issue: 10 Pages: 3017-27
  • DOI: 10.1002/stem.2058
  • Peer Reviewed
• [Journal Article] Synovial mesenchymal stem cells promote meniscus regeneration augmented by an autologous Achilles tendon graft in a rat partial meniscus defect model. (2015)
  • Author(s): Ozeki N, Muneta T, Matsuta S, Koga H, Nakagawa Y, Mizuno M, Tsuji K, Mabuchi Y, Akazawa C, Kobayashi E, Saito T, Sekiya I.
  • Journal Title: Stem Cells. Volume: 33(6) Issue: 6 Pages: 1927-38
  • DOI: 10.1002/stem.2030
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] P53 GENE REGULATES THE CELLULAR SENESCENCE OF MESENCHYMAL STEM/STROMAL CELLS (2018)
  • Author(s): Yo Mabuchi, Yuta Horiike, Eriko Suto Grace, Yusuke Ogata, Nobuharu Suzuki, Hayato Kaneda, Ryuji Okazaki, and Chihiro Akazawa
  • Organizer: International Society for Stem Cell Research
  • Int'l Joint Research
• [Presentation] 組織間葉系幹細胞の発生に関与する細胞集団の解析 (2017)
  • Author(s): 馬渕洋、小柳明日香、緒方勇亮、須藤絵里子グレース、鈴木喜晴、赤澤智宏
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台国際センター (宮城県・仙台市)
  • Year and Date: 2017-03-07
• [Presentation] Sox10を指標とした組織幹細胞の発生起源とその細胞集団の解析 (2017)
  • Author(s): 馬渕洋、小柳明日香、緒方勇亮、須藤絵里子グレース、鈴木喜晴、赤澤智宏
  • Organizer: 第３８回日本炎症・再生医学会
• [Presentation] Comparative analysis of mesenchymal stem/stromal cells in multiple organs. (2016)
  • Author(s): Yo Mabuchi, Chihiro Akazawa
  • Organizer: 先端モデル動物支援 若手技術講習会
  • Place of Presentation: 蓼科グランドホテル（長野県・茅野市）
  • Year and Date: 2016-09-14
• [Remarks] 東京医科歯科大学 大学院医歯学総合研究科 分子生命情報解析学分野
  • URL: http://akazawalab.com/
• [Remarks] 東京医科歯科大学 大学院保健衛生学研究科 分子生命情報解析学分野
  • URL: http://akazawalab.com/publication/
• [Remarks] 東京医科歯科大学 大学院保健衛生学研究科 分子生命情報解析学分野ホームページ
  • URL: http://akazawalab.com/
• [Remarks] http://akazawalab.com/publication/
• [Patent(Industrial Property Rights)] 移植効率を向上させるヒト間葉系幹細胞（MSC）の新鮮純化方法 (2017)
  • Inventor(s): 赤澤智宏、須藤絵里子グレース、馬渕洋
  • Industrial Property Rights Holder: 赤澤智宏、須藤絵里子グレース、馬渕洋
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017