Elucidation of the in vivo migration of mesenchymal stem cells.

• Project/Area Number: 24659789
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Plastic surgery
• Research Institution: Tokyo Medical University (2013); Keio University (2012)
• Principal Investigator: MATSUZAKI Yumi 東京医科大学, 医学部, 准教授 (50338183)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 間葉系幹細胞 / 創傷治癒学

Research Abstract

We report an improved prospective clonal isolation technique and reveal that the combination of three cell-surface markers (LNGFR, THY-1, and VCAM-1) allows for the selection of highly enriched clonogenic cells (one out of three isolated cells). Clonal characterization of LNGFR+THY-1+ cells demonstrated cellular heterogeneity among the clones. Rapidly expanding clones (RECs) exhibited robust multilineage differentiation and self-renewal potency, whereas the other clones tended to acquire cellular senescence via P16INK4a and exhibited frequent genomic errors. Furthermore, RECs exhibited unique expression of VCAM-1 and higher cellular motility compared with the other clones. The combination marker LNGFR+THY-1+VCAM-1hi+ (LTV) can be used selectively to isolate the most potent and genetically stable MSCs.

Research Products

• [Journal Article] Homeodomain transcription factor meis1 is a critical regulator of adult bone marrow hematopoiesis. (2014)
  • Author(s): Ariki R, Morikawa S, Mabuchi Y, Suzuki S, Nakatake M, Yoshioka K, Hidano S, Nakauchi H, Matsuzaki Y, Nakamura T, Goitsuka R.
  • Journal Title: PLoS One. Volume: 9 Issue: 2 Pages: 87646-87646
  • DOI: 10.1371/journal.pone.0087646
  • Peer Reviewed / Open Access
• [Journal Article] Twist2 functions as a tumor suppressor in murine osteosarcoma cells. (2013)
  • Author(s): Ishikawa T, Shimizu T, Ueki A, Yamaguchi S, Onishi N, Sugihara E, Kuninaka S, Miyamoto T, Morioka H, Nakayama R, Kobayashi E, Toyama Y, Mabuchi Y, Matsuzaki Y, Yamaguchi R, Miyano S and Saya H
  • Journal Title: Cancer Sci Volume: (in press) Issue: 7 Pages: 880-888
  • DOI: 10.1111/cas.12163
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells (2013)
  • Author(s): Ayano Kabashima-Niibe
  • Journal Title: Cancer Science Volume: 104 Issue: 2 Pages: 157-164
  • DOI: 10.1111/cas.12059
  • Peer Reviewed
• [Journal Article] Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest. (2013)
  • Author(s): Sowa Y, Imura T, Numajiri T, Takeda K, Mabuchi Y, Matsuzaki Y, Nishino K.
  • Journal Title: PLoS One. Volume: 8(12): Issue: 12 Pages: 84206-84206
  • DOI: 10.1371/journal.pone.0084206
  • Peer Reviewed
• [Journal Article] LNGFR+ Thy-1+ Vcam-1hi+ cells reveal functionally distinct subpopulations in mesenchymal stem cells (2013)
  • Author(s): Mabuchi Y Morikawa S, Harada S, Niibe K, Suzuki S, Renault-Mihara F, Houlihan DD, Akazawa C, Okano H, Matsuzaki Y
  • Journal Title: Stem Cell Reports Volume: 1(2) Pages: 152-165
  • Peer Reviewed
• [Journal Article] Cetuximab promotes anticancer drug toxicity in rhabdomyosarcomas with EGFR amplification in vitro (2013)
  • Author(s): Yamamoto Y, Fukuda K, Fuchimoto Y, Matsuzaki Y, Saikawa Y, Kitagawa Y, Morikawa Y, Kuroda T
  • Journal Title: Oncol Rep Volume: 30(3) Issue: 3 Pages: 1081-1086
  • DOI: 10.3892/or.2013.2588
  • Peer Reviewed
• [Journal Article] Basichelix-loop-helix transcriptional factor MyoR regulates BMP-7 in acute kidney injury. (2013)
  • Author(s): Kamiura N, Hirahashi J, Matsuzaki Y, Idei M, Takase O, Fujita T, TakatoT, Hishikawa K.
  • Journal Title: Am J Physiol RenalPhysiol. Volume: 304(9) Issue: 9 Pages: 2493-2500
  • DOI: 10.1152/ajprenal.00510.2012
  • Peer Reviewed
• [Journal Article] Kidney specific protein-positive cells derived from embryonic stem cells reproduce tubular structures in vitro and differentiate into renal tubular cells. (2013)
  • Author(s): Morizane R, Monkawa T, Fujii S, Yamaguchi S, Homma K, Matsuzaki Y, Okano H, Itoh H.
  • Journal Title: PLoS One. Volume: 8(6) Issue: 6 Pages: 64843-64843
  • DOI: 10.1371/journal.pone.0064843
  • Peer Reviewed
• [Journal Article] LNGFR+ Thy-1+ Vcam-1hi+ cells reveal functionally distinct subpopulations in mesenchymal stem cells. (2013)
  • Author(s): Mabuchi Y Morikawa S, Harada S; Niibe K, Suzuki S, Renault-Mihara F, Houlihan DD, Akazawa C, Okano H, *Matsuzaki Y.
  • Journal Title: Stem Cell Reports Volume: 1(2) Issue: 2 Pages: 152-165
  • DOI: 10.1016/j.stemcr.2013.06.001
  • Peer Reviewed
• [Journal Article] Isolation of mouse mesenchymal stem cells on the basis of expression of Sca-1 and PDGFR-α (2012)
  • Author(s): Houlihan DD, Mabuchi Y, Morikawa S, Niibe K, Araki D, Suzuki S, Okano H, Matsuzaki Y.(These authors contributed equally to this work.)
  • Journal Title: Nat Protoc Volume: 7(12) Issue: 12 Pages: 2103-2111
  • DOI: 10.1038/nprot.2012.125
  • Peer Reviewed
• [Journal Article] Transplantation of side population cells restores the function of damaged exocrine glands through clusterin (2012)
  • Author(s): Mishima K., Inoue H., Nishiyama T., Mabuchi Y., Amano Y., Ide F., Matsui M., Yamada H., Yamamoto G., Tanaka J., Yasuhara R., Sakurai T., Lee M., Chiba K., Sumimoto H., Kawakami Y., Matsuzaki Y., Tsubota K., Saito I
  • Journal Title: Stem Cells Volume: 30 Issue: 9 Pages: 1925-37
  • DOI: 10.1002/stem.1173
  • Peer Reviewed
• [Journal Article] Discovering the true identity and function of mesenchymal stem cells (2012)
  • Author(s): Mabuchi Y, Houlihan DD, Okano H and Matsuzaki Y
  • Journal Title: Inflammation and Regeneration Volume: 32 Issue: 4 Pages: 146-151
  • DOI: 10.2492/inflammregen.32.146
  • NAID: 130004943820
  • ISSN: 1880-8190, 1880-9693
  • Peer Reviewed
• [Presentation] 超高純度ヒトMSCの分離とその機能解析 (2014)
  • Author(s): 松崎有未
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] 間葉系幹細胞の体内動態と慢性GVHD誘導 (2014)
  • Author(s): 松崎有未
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] 超高純度ヒト間葉系幹細胞の解析『遊走能と未分化性維持』 (2013)
  • Author(s): 松崎有未
  • Organizer: 第34回日本炎症再生医学会
  • Place of Presentation: 国立京都国際会館
• [Presentation] 間葉系幹細胞の体内動態と慢性炎症惹起メカニズム (2013)
  • Author(s): 松崎有未
  • Organizer: 第12回日本再生医療学会学術集会
  • Place of Presentation: 横浜
• [Presentation] フローサイトメトリーによる間葉系幹細胞の分離 (2012)
  • Author(s): 松崎有未
  • Organizer: 日本免疫学会総会学術集会
  • Place of Presentation: 神戸
• [Presentation] Minor antigen-mismatched MSC react with residual host T cells to trigger the progression of chronic GVHD (2012)
  • Author(s): Yumi Matsuzaki
  • Organizer: International Society for Stem Cell Research 10th Annual Meeting
  • Place of Presentation: 横浜
• [Patent(Industrial Property Rights)] ヒト間葉系幹細胞の分離培養法 (2013)
  • Inventor(s): 松 崎有未、馬渕洋、岡野栄之
  • Industrial Property Rights Holder: 松崎有未
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013